Publications by authors named "Ishak Özel Tekin"

48 Publications

The comparison of pegylated liposomal doxorubicin and beta-carotene effects on JAR and JEG-3 choriocarcinoma human cell culture models

J Turk Ger Gynecol Assoc 2020 09 6;21(3):171-179. Epub 2020 Jul 6.

Clinic of Immunology, Zonguldak Bülent Ecevit University Health Practice and Research Hospital, Zonguldak, Turkey

Objective: The aim was to investigate the effectiveness of pegylated liposomal doxorubicin (PLD), beta-carotene, and a combination of PLD and beta-carotene on JAR and JEG-3 human choriocarcinoma (CC) cell lines for the treatment of CC.

Material And Methods: JAR and JEG-3 cells were cultured. PLD and beta-carotene trial groups were determined with different doses (for single drug trial; PLD 1, 2, 5 μg/mL and beta-carotene 1, 5, 10 μg/mL, and for combined drug trial; all PLD doses combined with beta-carotene 5 μg/mL). Drugs were administered to cultures simultaneously, and 72 hours later the cells were detached using trypsin-ethylenediamine tetraacetic acid solution. The percentage of apoptotic cells was determined by flow cytometry after annexin V staining. One set of the supernatant was collected before trypsin application to investigate beta-human chorionic gonadotropin (β-hCG) and hyperglycosylated hCG (H-hCG) levels. Statistical analyses of the apoptotic ratios were performed using Shapiro-Wilk, Kruskal-Wallis and Mann-Whitney U tests.

Results: Apoptosis increased in JAR and JEG-3 cultures after treatment with all doses of PLD (p<0.05). A single application of each betacarotene dose increased apoptosis in JAR cells (p<0.05) but had no apoptotic effects on JEG-3 cells. In the PLD and beta-carotene combination group, apoptosis increased in both JAR and JEG-3 cells (p<0.05).

Conclusion: To our knowledge, this is the first investigation of the effectiveness of PLD, beta-carotene, and PLD + beta-carotene combination therapy in two different CC cell lines. PLD is a promising chemotherapeutic drug, and beta-carotene can be used as a novel non-chemotherapeutic agent for treatment of CC. Based on the results of this study, vitamin A supplementation may have promise as a preventive measure. However, these data need support from animal experiments and clinical trials.
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http://dx.doi.org/10.4274/jtgga.galenos.2020.2019.0199DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7495128PMC
September 2020

Dendritic cell activation is blunted in patients with coronary artery disease and diabetes mellitus.

J Diabetes Complications 2019 02 23;33(2):134-139. Epub 2018 Nov 23.

Yenisehir Hospital Division of Cardiology, Mersin, Turkey. Electronic address:

Background: It has been shown that functional status of dendritic cells (DCs) in diabetic patients with unstable angina pectoris (UAP) are more mature and activated than diabetic patients without coronary artery disease (CAD) and none diabetic patients with UAP. Accordingly we aimed to assess the activation of DCs in patients with CAD with/and without Diabetes Mellitus (DM) and compare to those in subjects with normal coronary arteries (NCA).

Materials And Methods: Twenty three patients with severe CAD who were scheduled to coronary artery by-pass grafting surgery and 6 patients with angiographycally NCAs were included in the study. Activation of peripheral blood DCs have been analyzed by flow cytometric measures of CD86 activation.

Results: In patients with CAD and without DM, DC activation significantly increased after stimulation of oxidesized LDL (135 ± 121 vs 248 ± 197 p = 0.024). However this activation didn't significantly increased in patients with CAD and DM (100 ± 20 vs 120 ± 97, p = 0,54). Patients with NCAs and without DM showed marked activation of CD86 after stimulation with ox-LDL.

Conclusion: We have documented that DC activation, upon stimulation of ox-LDL has blunted in patients with CAD compared to patients with NCAs. Moreover this defective activation is more pronounced in those with diabetic patients with CAD.
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http://dx.doi.org/10.1016/j.jdiacomp.2018.11.004DOI Listing
February 2019

Bacterial cellulose as a new graft model for the Turkish delight technique in rhinoplasty: An experiment in 20 rats.

Ear Nose Throat J 2017 Sep;96(9):E1-E5

Department of Otolaryngology-Head and Neck Surgery, Faculty of Medicine, Bülent Ecevit University, 67600 Kozlu/Zonguldak/Türkiye.

We conducted an experiment to investigate the effectiveness of bacterial cellulose, a new graft material, in correcting and preventing dorsal nasal disorder in rhinoplasty. The experiment was performed on 20 Wistar albino rats. The rats were evenly divided into two groups: a fascia group and a cellulose group. In the fascia group, grafts from the conchal cartilage were removed, shredded, and then wrapped in temporal muscle fascia. In the cellulose group, shredded cartilage was wrapped in the bacterial cellulose. These shredded gristle grafts, which were also placed in a subcutaneous area at the back of the rats, were excised after 60 days. We then performed histopathology to compare the health and integrity of the cartilage and the degree of vascularization, fibrosis, and chronic inflammation in the two groups. We found a significantly greater degree of vascularization (p = 0.004) and fibrosis (p = 0.005) in the fascia group and a significantly greater degree of chronic inflammation (p = 0.023) in the cellulose group. We found no statistically significant difference between the two groups in terms of cartilage health and integrity. Our results suggest that bacterial cellulose grafting may play a role as an alternative to fascia grafting for the wrapping of shredded cartilages in Turkish delight grafting, but further investigation is needed.
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September 2017

Comparison of pharyngocutaneous fistula closure with and without bacterial cellulose in a rat model.

Auris Nasus Larynx 2018 Apr 6;45(2):301-305. Epub 2017 May 6.

Department of Otorhinolaryngology-Head and Neck Surgery, Pendik Training and Research Hospital, Marmara University Medical Faculty, Mimar Sinan Caddesi No. 41, Fevzi Cakmak Mahallesi, Ust Kaynarca-Pendik, 34899 Istanbul, Turkey.

Objective: The present study aimed to compare the effects of bacterial cellulose used for closure of pharyngocutaneous fistulae, a complication of total laryngectomy, with those of primary sutures in a rat model.

Methods: Thirty female Sprague-Dawley underwent experimental pharyngoesophagotomy and were grouped depending on the material used for pharyngocutaneous fistula closure: group I, which received primary sutures alone, group II, which received bacterial cellulose alone; and group III, which received both. After 7 days, the rats were sacrificed. Pharyngocutaneous fistula development was assessed, the gross wound was inspected, and histological examination was conducted.

Results: Pharyngocutaneous fistulae developed in 12 rats (41%) in all: 6 from group I (21%), 4 from group II (14%) and 2 from group III (7%).

Conclusion: Fibroblast density and inflammatory cell infiltration were significantly greater in group III than group I. We concluded that bacterial cellulose may be useful for pharyngocutaneous fistula closure.
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http://dx.doi.org/10.1016/j.anl.2017.04.005DOI Listing
April 2018

Red Cell Distribution Width Has a Predictable Value for Differentiation of Provoked and Unprovoked Venous Thromboembolism.

Indian J Hematol Blood Transfus 2016 Dec 12;32(4):481-487. Epub 2015 Dec 12.

Department of Immunology, Bulent Ecevit University School of Medicine, Zonguldak, Turkey.

Venous thromboembolism (VTE) is generally classified as provoked or unprovoked. This dichotomy is important for following patients, mortality rate, prognosis and whether more efficient therapy is needed. In VTE patients, during initial diagnosis, it is not known exactly whether red cell distribution width (RDW) have a predictable value for this differentiation and pathogenesis. In this study, 298 patients with VTE and 197 control subjects were included. Patients with VTE were defined as provoked or unprovoked with respect to physical examination findings and laboratory values. Changes in RDW were tested between VTE patients and control subjects, provoked and unprovoked VTE patients, and separately with control subjects. RDW was found to be high in provoked and unprovoked groups compared with control group ( < 0.001,  = 0.003 respectively). RDW was significantly high in provoked VTE patients group compared with unprovoked patients ( < 0.001) and a cut-off value was found to be 13.6 %. In ROC analysis, sensitivity was 90.19 % and specificity was 82 % (95 % CI 85.4-93. 8 % and 95 % CI 72.3-89. 6 % respectively). RDW could be used as a simple, costeffective and a reliable test independent of age in differentiation of provoked and unprovoked VTE. In order to better understand its role, prospective large homogenized population studies in different regions are necessary.
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http://dx.doi.org/10.1007/s12288-015-0626-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5074962PMC
December 2016

Concanavaline A conjugated bacterial polyester-based PHBHHx nanoparticles loaded with curcumin for breast cancer therapy.

J Microencapsul 2016 May 6;33(3):274-85. Epub 2016 Apr 6.

e Department of Chemistry, Biochemistry Division , Hacettepe University , Ankara , Turkey.

The aim of this study was to evaluate therapeutic potential of curcumin-loaded poly(3-hydroxybutyrate-co-3-hydroxyhexanoate) PHBHHx nanoparticles (CUR-NPs) and concanavaline A conjugated curcumin-loaded NPs (ConA-CUR-NPs) for breast cancer treatment. The size and zeta potential of prepared NPs were about 228 ± 5 nm and -23.3 mV, respectively. The entrapment efficiencies of polymer/drug weight ratios, 1.25CUR-NPs, 2.5CUR-NPs, 5CUR-NPs, ConA-1.25CUR-NPs, ConA-2.5CUR-NPs and ConA-5CUR-NPs were found to be ≈68, 55, 45, 70, 60 and 51%, respectively. Optimized NPs formulations in the freeze-dried form were assessed with their short-term stability for 30 days of storage at 4 °C and 25 °C. Anticancer activity of ConA-CUR-NPs was proved by MTT assay and reconfirmed by double staining and flow cytometry results. The anticancer activity of ConA-CUR-NPs was measured in human breast cancer cells (MDA-MB 231) in vitro, and the results revealed that the ConA-CUR-NPs had better tumor cells decline activity.
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http://dx.doi.org/10.3109/02652048.2016.1169325DOI Listing
May 2016

Comparison of the diagnostic value of different lymphocyte subpopulations in bronchoalveolar lavage fluid in patients with biopsy proven sarcoidosis.

Sarcoidosis Vasc Diffuse Lung Dis 2016 Jan 15;32(4):305-12. Epub 2016 Jan 15.

Bülent Ecevit University Faculty of Medicine Department of Chest diseases.

Background: Bronchoalveolar lavage is considered a helpful tool in the diagnosis of diffuse parenchimal lung diseases such as sarcoidosis. CD4/CD8 ratio is higly specific but not sensitive to distinguish sarcoidosis and other intestitial lung diseases. We aimed to compare the diagnostic value of CD4/CD8 ratio and other lmphocyte subpopulations such as CD3+16+56, CD103+, CD4+CD103+, CD8+CD103+ in bronchoalveolar lavage to distinguish sarcoidosis and other nonsarcoidosis interstitial lung diseases.

Methods: Using the bronchoscopy records from 2006 to 2013, we evaluated 68 patients with biopsy proven sarcoidosis and 72 patients with clinicoradiological and/or biopsy proven diffuse parenchimal lung diseases. Cut off values, sensitivity and specificity were given for aforementioned parameters.

Results: Bronchoalveolar lavage CD4/CD8 ratio, CD4+ T lymphocyte percentage, CD4+103+, CD3+CD103-, CD8+CD103+/CD103+ ratio were significantly higher in sarcoidosis than other diffuse parenchimal lung diseases whereas CD3+103+, CD3+16+56+, CD8+, CD8+CD103+, CD8+CD103+/CD8+ were significantly lower. Best cut off value of CD4/CD8 was 1.34 with sensitivity and specificity 76.4%, 79.4% respectively. The cut off values of CD4/CD8 of >3.5 and >2.5 had specificity 95.9% and 95.3%, respectively and sensitivity 52%, 41%, respectively.

Conclusion: CD4/CD8 ratio is highly specific but not sensitive for sarcoidosis diagnosis. Thus, BAL flow cytometry is not diagnostic alone without appropriate clinicoradiological and/or histopathological findings.
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January 2016

DNA studies of newly synthesized heteroleptic platinum(II) complexes [Pt(bpy)(iip)](2+) and [Pt(bpy)(miip)](2.).

J Biol Inorg Chem 2016 Apr 1;21(2):163-75. Epub 2015 Dec 1.

Department of Immunology, Faculty of Medicine, Bulent Ecevit University, 67100, Zonguldak, Turkey.

Two new mono-nuclear heteroleptic platinum(II) complexes, [Pt(bpy)(iip)](PF6)2 (1) and [Pt(bpy)(miip)](PF6)2·2H2O (2) (bpy is 2,2'-bipyridine; iip is 2-(imidazo-4-yl)-1H-imidazo[4,5-f] [1,10] phenanthroline; miip is 2-(1-methylimidazo-2-yl)-1H-imidazo[4,5-f] [1, 10] phenanthroline), have been synthesized and fully characterized by CHN analysis, electrospray ionization and MALDI-TOF mass spectrometry, (1)H NMR, FT-IR (ATR), and UV-Vis spectrophotometer. Cytotoxicity, ability to inhibit DNA transcription and DNAse activity of the complexes were studied. The DNA-binding behaviors of both complexes have also been studied by spectroscopic methods, cyclic voltammetry and viscosity measurements. Both complexes showed cytotoxic properties and 2 was more cytotoxic than 1. DNA transcription was inhibited upon increasing concentrations of both complexes. The complex 2 was found to be a better inhibitor than 1. The same pattern can be seen in the DNAse profile of the complexes. In addition, 2 was found to promote cleavage of pBR322 DNA at a lower concentration than 1. The spectroscopic, electrochemical and viscometric results indicate that both complexes show some degree of binding to DNA in an intercalative mode, resulting in intrinsic binding constants K b = 3.55 ± 0.6 × 10(4) M(-1) and 7.01 ± 0.9 × 10(4) M(-1) for 1 and 2, respectively. The difference in the DNA-binding affinities of 1 and 2 may presumably be explained by the methylated imidazole nitrogen atom that makes the compound more hydrophobic and gives better intercalative binding ability to DNA's hydrophobic environment.
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http://dx.doi.org/10.1007/s00775-015-1317-8DOI Listing
April 2016

Bronchoalveolar Lavage Fluid Characteristics of Patients With Sarcoidosis and Nonsarcoidosis Interstitial Lung Diseases: Ten-Year Experience of a Single Center in Turkey.

Iran Red Crescent Med J 2015 Oct 28;17(10):e31103. Epub 2015 Oct 28.

Department of Chest Diseases and Tuberculosis, Faculty of Medicine, Bulent Ecevit University, Zonguldak, Turkey.

Background: Bronchoalveolar lavage (BAL) is a noninvasive and useful technique for evaluating interstitial lung diseases (ILDs). Flow cytometric analysis of BAL fluid reveals specific diagnostic information in some unusual ILDs, and helps to narrow down the possible causes of interstitial diseases in most patients with more common disorders. A high BAL CD4/CD8 ratio is highly specific for sarcoidosis but can also be seen in other ILDs.

Objectives: In this retrospective, descriptive, cross-sectional study, we compared BAL fluid characteristics and clinical variables in patients with sarcoidosis and non-sarcoidosis ILDs in a large cohort.

Patients And Methods: The study was conducted in a tertiary university hospital in Zonguldak, the biggest city of the western Black Sea region of Turkey. Between 2004 and 2014, all patients who underwent both fiberoptic bronchoscopy and BAL with a suspicion of ILD were included in the study, retrospectively. Patients were divided into two main groups: sarcoidosis and non-sarcoidosis ILDs. Non-sarcoidosis ILDs were further divided into subgroups: pneumoconiosis, tuberculosis (TB), collagen vascular diseases, idiopathic interstitial pneumonias, malignancies, and unclassified ILDs. The clinical data of patients, including age, gender, smoking status, pulmonary function tests, and BAL flow cytometric analysis results, were compared among groups.

Results: In total, 261 patients (119 sarcoidosis and 142 non-sarcoidosis ILDs) were enrolled. The median (interquartile range) BAL CD4/CD8 ratio and lymphocyte fraction were significantly higher in sarcoidosis than in non-sarcoidosis ILDs: 3.88 (3.76) versus 0.88 (1.01), respectively, and 20.6 (28.3) versus 6.0 (13.7), respectively. T cell receptor γ delta, CD16(+)56(+), CD103(+), CD8(+)103(+), and CD3(+)16(+)56(+) cells were significantly lower in sarcoidosis than in non-sarcoidosis ILDs. The median BAL CD4/CD8 ratios were significantly higher in patients with TB (1.87, P = 0.01) and malignancies (1.69, P = 0.03) than in other non-sarcoidosis ILDs.

Conclusions: Among BAL fluid flow cytometric parameters, CD4/CD8 and lymphocyte fraction may be helpful for distinguishing sarcoidosis from other ILDs, but they are neither specific nor diagnostic for any lung disease. Thus, a multidisciplinary diagnostic discussion is required to differentiate various ILDs.
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http://dx.doi.org/10.5812/ircmj.31103DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4636855PMC
October 2015

The influence of cisplatin, doxorubicin, pegylated doxorubicin, oxaliplatin and gemcitabine on mahlavu cell line.

J BUON 2015 Mar-Apr;20(2):608-13

Bulent Ecevit University, Faculty of Medicine, 1Department of Internal Medicine, Zonguldak, Turkey.

Purpose: Hepatocellar carcinoma (HCC) remains a major health problem being the third leading cause of deaths due to cancer worldwide. Because HCC is known to be highly resistant to conventional systemic therapies, single-agent or combination of systemic therapies have been investigated. Today, sorafenib, a multikinase inhibitor, is the only approved systemic agent for the first line treatment of advanced HCC. In this study, we aimed to investigate the influence of different concentrations of cisplatin, doxorubicin, pegylated doxorubicin (PLD), oxaliplatin and gemcitabine by applying these agents either single or in combinations on mahlavu cell line.

Methods: HCC mahlavu cell line was used for the experiments. Cell death was measured by flow cytometry at 48 hrs after incubation with various concentrations (0.1 μg/ml, 1.0 μg/ml and 10 μg/ml) of the drugs.

Results: Cell death due to gemcitabine was found to be significantly higher than cell deaths caused by the other single agents including cisplatin, oxaliplatin, doxorubicin and PLD (p<0.001, p<0.001, p<0.001 and p=0.0049, respectively). There was no significant difference between gemcitabine and both the gemcitabine combination with doxorubicin and PLD (p=0.992 and p=0.441, respectively).

Conclusion: This is a preliminary analysis evaluating the effect of the conventional chemotherapeutic agents on mahlavu cell line in vitro. The findings of this study suggest that gemcitabine-based therapies keep on being the prefered therapeutic approach for the treatment of HCC.
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July 2015

Mediators of gut mucosal immunity and inflammation.

Mediators Inflamm 2015 19;2015:765303. Epub 2015 Apr 19.

Department of Molecular Genetics, Maastricht University (MUMC), Universiteitssingel 50, 6229 ER Maastricht, Netherlands.

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http://dx.doi.org/10.1155/2015/765303DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4417598PMC
February 2016

Elevated chemokine levels during adult but not pediatric Crimean-Congo hemorrhagic fever.

J Clin Virol 2015 May 14;66:76-82. Epub 2015 Mar 14.

Department of Paediatric Infectious Diseases, School of Medicine, Hacettepe University, Ankara, Turkey.

Background: Crimean-Congo hemorrhagic fever (CCHF) is a tick-borne viral zoonosis. Clinical reports indicate the severity of CCHF is milder in children than adults. The chemokines are important chemo-attractant mediators of the host immune system.

Objectives: The main aim of the study was to identify whether or not there were any differences in chemokine levels between the pediatric and adult patients and control groups, and whether there was any correlation with disease severity.

Study Design: The serum levels of select chemokines including chemokine (C-C) ligand 2 (CCL2), CCL3, CCL4, chemokine (C-X-C) ligand 8 (CXCL8), CXCL9, and granulocyte-colony stimulating factor (G-CSF) in 29 adult and 32 pediatric CCHF patients and in 35 healthy children and 40 healthy adult control groups were studied by flow cytometric bead immunoassay method.

Results: Great variability was detected in the serum levels of the chemokines for both the adult and pediatric patients and controls. With the exception of G-CSF, the median serum levels of CCL2, CCL3, CCL4, CXCL8, and CXCL9 were found to be significantly higher in the adult patients compared to adult controls (2364.7 vs. 761 pg/ml; 714.1 vs. 75.2 pg/ml; 88.6 vs. 25.5 pg/ml; 217.9 vs. 18.3 pg/ml; 875 vs. 352.2 pg/ml, respectively, p < 0.0001 for all comparisons). Among the chemokines the median CCL4 and G-CSF levels were significantly higher in the pediatric patients compared to pediatric controls (40.3 vs. 7.1 pg/ml, p < 0.0001; 0.1 vs. 0.1 pg/ml, p = 0.049, respectively).

Conclusion: The results of this study showed prominent chemokine raising in adult CCHF patients compared to children CCHF patients.
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http://dx.doi.org/10.1016/j.jcv.2015.03.010DOI Listing
May 2015

Cystain C and neuropeptid Y levels in brain tissues after experimental subarachnoid hemorrhage.

Acta Biochim Pol 2014 18;61(4):825-8. Epub 2014 Dec 18.

Department Neurosurgery, Bülent Ecevit University (Formerly, Zonguldak Karaelmas University), Zonguldak, Turkey.

The aim of this study was to investigate the changes in the levels of cystatin C, which protects neurodegeneration in the central nervous system with the inhibition of cysteine protease and by inducing autophagy in the pathogenesis of cerebral vasospasm and levels of vasoconstrictive neuropeptid Y (NPY) in the brain tissue homogenates of rat model of subarachnoid hemorrhage (SAH). Three experimental groups were used: Day 2 and Day 7 groups after SAH, and also a control group. There were seven Wistar albino rats in each group. SAH was accomplished by transclival basilar artery puncture. Rat cystatin C, rat NPY were determined with ELISA in brain tissue homogenates. Day 2 group showed significantly enhanced cystatin C values in comparision with the control group (P=0.048). NPY levels between the Day 2 and Day 7 groups and the control groups were not significantly different (P=0.315). In histopathological examination, there was less neuronal loss in the Day 2 group than in the Day 7 group. Regarding our results, it would be more valuable to measure NPY levels in specific brain areas. The increased cystatin C levels on the second day after SAH is probably a pathophysiologic mechanism to organize protease activity.
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September 2015

Apoptosis and necrosis in the circumventricular organs after experimental subarachnoid hemorrhage as detected with annexin V and caspase 3 immunostaining.

Neurol Res 2014 Dec 19;36(12):1114-20. Epub 2014 Aug 19.

Objectives: The circumventricular organs (CVOs) are essential for most autonomic and endocrine functions. Trauma and bleeding can affect their function. The aim of this study was to investigate apoptosis and necrosis in CVOs in the early period after experimental subarachnoid hemorrhage (SAH) in rats, using annexin V affinity and caspase 3 immunostaining.

Methods: Three experimental groups were used: Days 1 and 2 after SAH, and a control group, seven Wistar albino rats each. Subarachnoid hemorrhage was accomplished by transclival basilar artery puncture. Rats were perfused with 0.9% NaCl and 0·1M phosphate buffer pH 7.4 until heart stoppage. Apoptosis and necrosis in CVOs were measured by flow cytometry with annexin V staining, and by caspase 3 immunostaining.

Results: Apoptosis in the organum vasculosum lamina terminalis (OVLT), median eminence (ME), and area postrema (AP) was significantly higher in the Day 1 group than in the control group. Apoptosis in the subfornicial organ (SFO), OVLT, ME, and AP was significantly higher in the Day 2 group than in the control group. There were significant differences between the Day 1 and Day 2 groups, except for AP. Necrosis in SFO and OVLT was significantly higher in the Day 2 group than in the Day 1 or control groups, whereas necrosis in the ME and AP did not differ between the three groups. Caspase 3-positive cell density was more intense in the Day 2 group than in the Day 1 and control groups.

Discussion: Prevention of apoptosis may potentially improve impaired functions of CVOs after SAH.
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http://dx.doi.org/10.1179/1743132814Y.0000000437DOI Listing
December 2014

Ischemia modified albumin increase indicating cardiac damage after experimental subarachnoid hemorrhage.

BMC Neurosci 2014 Feb 24;15:33. Epub 2014 Feb 24.

Department of Biochemistry, Faculty of Medicine, Bülent Ecevit University (Formerly, Zonguldak Karaelmas University), 67630, Esenköy, Kozlu, Zonguldak, Turkey.

Background: Cardiac complications are often developed after subarachnoid hemorrhage (SAH) and may cause sudden death of the patient. There are reports in the literature addressing ischemia modified albumin (IMA) as an early and useful marker in the diagnosis of ischemic heart events. The aim of this study is to evaluate serum IMA by using the albumin cobalt binding (ACB) test in the first, second, and seventh days of experimental SAH in rats.Twenty-eight Wistar albino rats were divided into four groups each consisting of seven animals. These were classified as control group, 1st, 2nd and 7th day SAH groups. SAH was done by transclival basilar artery puncture. Blood samples were collected under anesthesia from the left ventricles of the heart using the cardiac puncture method for IMA measurement. Histopathological examinations were performed on the heart and lung tissues. Albumin with by colorimetric, creatine kinase (CK), aspartate aminotransferase (AST), lactate dehydrogenase (LDH) were determined on an automatic analyser using the enzymatic method. IMA using by ACB test was detected with spectrophotometer.

Results: Serum IMA (p = 0.044) in seventh day of SAH were higher compared to the control group. Total injury scores of heart and lung tissue, also myocytolysis at day 7 were significantly higher than control group (p = 0.001, p = 0.001, p = 0.001), day 1 (p = 0.001, p = 0.001, p = 0.001) and day 2 (p = 0.001, p = 0.007, p = 0.001). A positive correlation between IMA - myocytolysis (r = 0.48, p = 0.008), and between IMA - heart tissue total injury score (r = 0.41, p = 0.029) was found.

Conclusion: The results revealed that increased serum IMA may be related to myocardial stress after SAH.
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http://dx.doi.org/10.1186/1471-2202-15-33DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3936857PMC
February 2014

Prognostic significance of peripheral blood flow cytometry parameters in patients with non-metastatic breast cancer.

Asian Pac J Cancer Prev 2013 ;14(12):7645-9

Department of Medical Oncology, School of Medicine, Bulent Ecevit University, Zonguldak, Turkey E-mail :

Background: Immune functions and their relation to prognosis in breast cancer patients have become areas of great interest in recent years. Correlations between survival outcomes and peripheral blood flow cytometry parameters are therefore of interest. Here we focused on patients with non-metastatic breast cancer (BC).

Materials And Methods: A total of 29 patients with pathological confirmed breast carcinoma and flow cytometry data were assessed for overall survival (OS) and progression free survival (PFS).

Results: The median age of the patients was 54 years (range, 29-83). Multivariate analysis revealed that OS was significantly associated with absolute cytotoxic T cell count (95%CI, coef 2.26, p=0.035), tumor size (95%CI, coef -14.5, p 0.004), chemotherapy (95%CI, coef 12.9, p 0.0001), MFI of CD4 (95%CI, coef -5.1, P 0.04), MFI of HLA DR (95%CI, coef -5.9, p 0.008) and tumor grade (95%CI, coef -13, P 0.049) with R-Sq(adj)=67%. Similar findings were obtained for PFS.

Conclusions: OS and PFS were significantly associated with tumor grade, tumor size, chemotherapy, MFI of CD4, HLA DR and absolute cytotoxic T cell count. The study revealed that MFI of basic CD markers and absolute cytotoxic T cell number may be a prognostic factors in women with non-metastatic BC.
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http://dx.doi.org/10.7314/apjcp.2013.14.12.7645DOI Listing
September 2014

Oxidized LDL in inflammation: from bench to bedside.

Mediators Inflamm 2013 24;2013:762759. Epub 2013 Nov 24.

Department of Molecular Genetics, Maastricht University (MUMC), Universiteitssingel 50, 6229 ER, Maastricht, The Netherlands.

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http://dx.doi.org/10.1155/2013/762759DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3857732PMC
October 2014

Autologous Serum Skin Test versus Autologous Plasma Skin Test in Patients with Chronic Spontaneous Urticaria.

Dermatol Res Pract 2013 9;2013:267278. Epub 2013 Jul 9.

Bulent Ecevit University, School of Medicine, Department of Dermatology, Kozlu, 67600 Zonguldak, Turkey.

Previous studies indicate that 25-45% of chronic urticaria patients have an autoimmune etiology. Autologous serum skin test (ASST) and autologous plasma skin test (APST) are simple tests for diagnosing chronic autoimmune urticaria (CAU). However, there are still some questions about the specificity of these tests. This study consisted of 50 patients with chronic spontaneous urticaria (CSU) and 50 sex- and age-matched healthy individuals aged 18 years, and older. A total of 31 (62%) patients and 5 (10%) control patients had positive ASST; 21 (42%) patients and 3 (6%) control patients had positive APST. Statistically significant differences were noted in ASST and APST positivity between the patient and control groups (ASST P < 0.001; APST P < 0.001). Thirteen (26%) patients and 5 (10%) control patients had antithyroglobulin antibodies or antithyroid peroxidase antibody positivity. No statistically significant differences were noted in thyroid autoantibodies between the patient and control groups (anti-TG P = 0.317; anti-TPO P = 0.269). We consider that the ASST and APST can both be used as in vivo tests for the assessment of autoimmunity in the etiology of CSU and that thyroid autoantibodies should be checked even when thyroid function tests reveal normal results in patients with CSU.
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http://dx.doi.org/10.1155/2013/267278DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3722846PMC
August 2013

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

Plasma concentrations of angiopoietin-1, angiopoietin-2 and Tie-2 in colon cancer.

Eur Cytokine Netw 2012 Jun;23(2):68-71

Karaelmas University, Department of Internal Medicine, Division of Medical Oncology, Zonguldak-Turkey.

Background/aim: despite the rapidly accumulating histopathological data reporting differences in the expression of members of the angiopoietin family on the surface of various normal and tumour cells, data for these growth factors in plasma from cancer patients, including colon cancer, are scarce. The aims of the present study were to measure the plasma concentrations of Ang-1, Ang-2 and Tie-2 in colon cancer patients, and to assess the correlation between the concentrations of these factors and the stage of the tumor.

Patients And Methods: the study cohort included 36 patients (18 male, 18 female) with colon cancer (mean age 52.6 ± 15.0), and 36 sex- and age-matched, healthy controls who were free of inflammatory, neoplastic, atherosclerotic and connective tissue disease, recruited from hospital staff and attendees at hospital for check-up. Concentrations of Ang-1, Ang-2 and Tie-2 were measured using the enzyme-linked immunosorbent assay (ELISA) method.

Results: concentrations of Ang-2 (median 3,188.0 pg/mL, min: 1,070.5-max: 5,765.5) and Tie-2 (median 22 ng/mL, min:12-max:46) were significantly higher in patients with colon cancer, while concentrations of Ang-1 were not statistically different between the groups. Furthermore, concentrations of Ang-2 (median 4,292.0 pg/mL, min: 3,090.0-max: 5,765.5) were found to be significantly higher in stage III patients compared to stage II patients, whereas no difference was found between the concentrations of Ang-1 and Tie-2 in different colon cancer stages.

Conclusion: plasma concentrations of Ang-1, Ang-2 and Tie-2 may be valuable, additional, tumor markers in colon cancer that should be tested in further trials.
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http://dx.doi.org/10.1684/ecn.2012.0308DOI Listing
June 2012

Plasma concentrations of Ang-1, Ang-2 and Tie-2 in gastric cancer.

Eur Cytokine Netw 2012 Mar;23(1):21-4

Karaelmas University, Department of Internal Medicine, Division of Medical Oncology, Zonguldak, Turkey.

Background/aim: Ang-1 and Ang-2 have both been identified as ligands for Tie-2, a receptor expressed on endothelial cells (EC). They play critical roles in angiogenesis, in concert with VEGF. Ang-1-binding to Tie-2 maintains and stabilizes mature vessels by promoting interactions between EC and the surrounding extra-cellular matrix. However, Ang-2 shows context-dependent, proangiogenic and antiangiogenic activities. Despite the rapidly accumulating histopathological data reporting differences in the expression of members of the Ang family on the surface of various normal and tumour cells, data for these growth factors in plasma from cancer patients, including gastric cancer, remain scarce. The aims of the present study were to measure the plasma concentrations of Ang-1, Ang-2 and Tie-2 in gastric cancer patients, and to assess the correlation between the concentrations of these factors and the stage of the tumor.

Patients And Methods: The study cohort consisted of 50 patients (33 male, 17 female) with gastric cancer, ranging in age from 38 to 74 years (mean age 55.3±12.4), and 50 sex- and age-matched, healthy controls. Determinations of Ang-1, Ang-2 and Tie-2 were performed using the enzyme-linked immunosorbent assay (ELISA) method.

Results: Concentrations of Ang-2 and Tie-2 were significantly higher in patients with gastric cancer than controls, while concentrations of Ang-1 were not statistically different between the groups. Concentrations of Ang-1, Ang-2 and Tie-2 were not statistically significantly different in gastric cancer patients with different stages of disease.

Conclusion: Ang-2 and Tie-2 plasma concentrations might be useful, additional tumor markers in gastric cancer.
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http://dx.doi.org/10.1684/ecn.2012.0301DOI Listing
March 2012

The presence of oxidized low-density lipoprotein and inducible nitric oxide synthase expression in renal damage after intestinal ischemia reperfusion.

Kaohsiung J Med Sci 2012 Jan 11;28(1):16-22. Epub 2011 Dec 11.

Department of Pathology, Faculty of Medicine, Zonguldak Karaelmas University, Zonguldak, Turkey.

Intestinal ischemia/reperfusion (I/R) is a complex phenomenon that causes destruction of both local and remote tissues. The objective of this study was to investigate the possible participation of oxidized low-density lipoproteins (oxLDLs) and inducible nitric oxide synthase (iNOS) expression in renal tissue damage after intestinal I/R. The superior mesenteric artery was blocked for 30 minutes, followed by 24 hours of reperfusion. At the end of the reperfusion period, renal tissues were removed; the presence of oxLDL, superoxide dismutase enzyme activity, malondialdehyde levels, and iNOS expression were evaluated. I/R resulted in positive oxLDL staining in renal tissue. Compared with control rats, tissue from the I/R group showed significantly higher malondialdehyde levels and lower superoxide dismutase enzyme activity. Strong and diffuse iNOS expression was present in the I/R group. Our findings support the hypothesis that I/R of intestinal tissue results in oxidative and nitrosative stress and enhances lipid peroxidation in the end organ. These data show that oxLDL accumulates in rat renal tissue after intestinal I/R. Antioxidant strategies may provide organ protection in patients with reperfusion injury, at least by affecting interactions with free radicals, nitric oxide, and oxLDL. This study demonstrates for the first time that oxLDL may play a role in renal tissue damage after intestinal I/R. Antioxidant strategies may be beneficial for protection from reperfusion injury.
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http://dx.doi.org/10.1016/j.kjms.2011.06.030DOI Listing
January 2012

Helicobacter pylori eradication lowers serum asymmetric dimethylarginine levels.

Mediators Inflamm 2010 13;2010:685903. Epub 2010 Dec 13.

Department of Gastroenterology, Faculty of Medicine, Zonguldak Karaelmas University, 67800 Zonguldak, Turkey.

Introduction: Microbial pathogens, one of them is Helicobacter pylori (H. pylori), have frequently been implicated in the atherogenesis. Endothelium-derived nitric oxide (NO) is synthesized from L-arginine by nitric oxide synthase (NOS) and plays a pivotal role in the regulation of vascular tone. Asymmetric dimethylarginine (ADMA) is the most potent endogenous NOS inhibitor. Elevated levels of ADMA have been reported in many circumstances associated with a high cardiovascular risk. The aim of the present study was to investigate whether the eradication of H. pylori infection affects serum ADMA levels.

Materials And Methods: Forty-two H. pylori-positive patients were enrolled in the study. Triple therapy for 14 days were given to all patients. Serum ADMA levels were measured at baseline and 2 months after therapy.

Results: Eradication was achieved in 34 (81%) patients. The mean serum ADMA levels before and after therapy were 1, 77 ± 0, 30 and 1, 67 ± 0, 29 ng/mL in the group with H. pylori eradicated and 1, 63 ± 0, 28 and 1, 56 ± 0, 32 ng/mL in the noneradicated, respectively. We detected statistically significant decreased serum ADMA levels after therapy in H. pylori eradicated group.

Conclusion: These findings have indicated that eradication of H. pylori infection may decrease the risk of atherosclerosis and cardiovascular events.
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http://dx.doi.org/10.1155/2010/685903DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3010707PMC
April 2011

Effects of pegylated interferon α on fibrinolytic parameters in patients with chronic hepatitis C.

Clin Appl Thromb Hemost 2011 Oct 10;17(5):449-53. Epub 2010 Aug 10.

Division of Hematology, Department of Internal Medicine, Karaelmas University, Faculty of Medicine, Zonguldak, Turkey.

Interferon (IFN) interacts with endothelial cells and modulates the functions of these cells. In our study, we aimed to determine the effects of treatment with pegylated IFN-α (peg-IFN-α) on fibrinolytic parameters in patients with chronic hepatitis C. Fifteen patients with chronic hepatitis C were treated with peg-IFN-α once per week plus daily oral ribavirin. Euglobulin lysis time (ELT), plasma levels of D-dimer, tissue-type plasminogen activator (t-PA), plasminogen activator inhibitor 1 (PAI-1), and thrombin activatable fibrinolysis inhibitor (TAFI) were determined before treatment, 2 weeks, 1 month, and 3 months after the initiation of the treatment. Plasma levels of t-PA increased significantly 1 month and 3 months after the treatment (P < .05). The PAI-1 and TAFI levels in 2 weeks, 1 month and 3 months after treatment were not statistically different as compared with pretreatment levels (P > .05) No significant difference in plasma D-dimer levels was observed during peg-IFN-α treatment (P > .05). There was a significant decrease in ELT 1 month and 3 months after the treatment (P < .05). Our results indicated that treatment with peg-IFN-α may be associated with enhanced fibrinolysis.
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http://dx.doi.org/10.1177/1076029610371475DOI Listing
October 2011

Further increase in the expression of activation markers on monocyte-derived dendritic cells in coronary artery disease patients with ectasia compared to patients with coronary artery disease alone.

Mediators Inflamm 2010 14;2010:748919. Epub 2010 Jun 14.

Department of Cardiology, Faculty of Medicine, Zonguldak Karaelmas University, Zonguldak, Turkey.

Background: Coronary artery ectasia (CAE) is defined as localized or diffuse dilation of the coronary arteries. There are scarce data about the role of dendritic cells in CAE development. In this study we investigated the activation markers on the surface of monocyte-derived dendritic cells (mDCs) in coronary artery disease (CAD) patients with or without CAE.

Method: The study consisted of 6 patients who had obstructive CAD with CAE, 6 CAD patients without CAE and 6 subjects with angiographically normal coronary arteries. mDCs were cultivated from peripheral blood monocytes. Surface activation markers were detected by flow cytometry.

Results: CAD patients with CAE were detected to have significantly higher mean fluorescence intensities of CD11b, CD11c, CD54 , CD83, CD86 and MHC Class II molecules on mDCs in comparison to CAD patients without CAE and normal controls (P < .001 for all). A significant positive correlation was found between the number of vessels with CAE and the levels of CD11c, CD86, and MHC Class II molecules.

Conclusion: mDCs display an increased cell surface concentration of activation molecules in CAD patients with CAE compared to patients with CAD alone. DC activation may play an important role for CAE development in patients with CAD.
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http://dx.doi.org/10.1155/2010/748919DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2902079PMC
October 2010

The levels of tumor necrosis factor-alpha and interleukin-6 in patients with isolated coronary artery ectasia.

Mediators Inflamm 2009 17;2009:106145. Epub 2009 Jun 17.

Department of Cardiology, School of Medicine, Zonguldak Karaelmas University, Kozlu, Zonguldak, Turkey.

Background/aim: Coronary artery ectasia (CAE) is considered as a variant of atherosclerosis. Tumor necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6) are among the sensitive markers of systemic inflammation. The aim of this study was to evaluate the plasma levels of the cytokines; TNF-alpha and IL-6 in CAE patients.

Methods: Plasma concentrations of TNF-alpha and IL-6 were measured in 36 patients with CAE (28 males, mean age: 58.2 +/- 12 years), and results were compared with age and sex-matched controls (n = 32) without coronary artery ectasia. TNF-alpha and IL-6 concentrations in blood were assessed by enzyme-linked immunosorbent assay (ELISA).

Results: Baseline characteristics of the two groups were similar. TNF-alpha and IL-6 levels were significantly higher in CAE group than controls (15.6 +/- 11.2 pg/mL versus 7.8 +/- 3.7 pg/mL, P < .001, and 17.2 +/- 12.6 versus 7.6 +/- 2.1 P < .0001, resp.).

Conclusion: CAE patients showed increases in TNF-alpha and IL-6 levels compared to the controls. This study provides evidence for alterations in the proinflammatory cytokines which suggest the involvement of the immune system in the pathophysiology of CAE. Further placebo-controlled studies are needed to evaluate the clinical significance of this increase in TNF-alpha and IL-6 levels.
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http://dx.doi.org/10.1155/2009/106145DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2699491PMC
September 2009

Low-density lipoproteins oxidized after intestinal ischemia/reperfusion in rats.

J Surg Res 2009 Nov 6;157(1):e47-54. Epub 2008 Dec 6.

Department of Immunology, Zonguldak Karaelmas University, Turkey.

Background: Intestinal ischemia/reperfusion (I/R) is a complex phenomenon causing destruction of both local and remote tissues, as well as multiple-organ failure. We investigated the role of lipid peroxidation in damage to intestinal, liver, and lung tissues in this pathology.

Materials And Methods: The superior mesenteric artery was blocked for 30 min followed by 24 h of reperfusion. Tissues were removed and the presence of oxidized LDL, the activities of the superoxide dismutase enzyme, malondialdehyde levels, and inducible nitric oxide synthase expression were each evaluated in the intestinal, liver, and lung tissues.

Results: While there was no staining in the control group tissues, ischemia/reperfusion resulted in positive oxidized LDL staining in all of the I/R test group tissue samples. Inducible nitric oxide synthase expression was significantly increased in the ischemia/reperfusion group tissues. Compared with those of the control group rats, the ischemia/reperfusion group tissues showed significantly higher malondialdehyde levels and lower superoxide dismutase activities.

Conclusions: This study demonstrated for the first time that oxidized LDL accumulated in the terminal ileum, liver, and lung tissues after intestinal ischemia/reperfusion. This occurrence (or the presence of oxidized LDL) may be an indicator of ongoing oxidative stress and enhanced lipid peroxidation. Augmentation of inducible nitric oxide synthase expression may play a role in progression of inflammation and LDL oxidation. These data support the hypothesis that cellular oxidative stress is a critical step in reperfusion-mediated injury in both the intestine and end organs, and that antioxidant strategies may provide organ protection in patients with reperfusion injury, at least through affecting interaction with free radicals, nitric oxide, and oxidized LDL.
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http://dx.doi.org/10.1016/j.jss.2008.11.006DOI Listing
November 2009

Erythropoietin: a possible cytoprotective cytokine in acute necrotizing pancreatitis.

J Hepatobiliary Pancreat Surg 2009 31;16(4):530-7. Epub 2009 Mar 31.

Zonguldak Karaelmas University, School of Medicine, Zonguldak, Turkey.

Background/purpose: Despite decades of research and clinical trials, a specific therapeutic treatment for acute pancreatitis (AP) has yet to be developed. The aim of the present study was to investigate the effects of erythropoietin on the severity of taurocolic acid-induced acute necrotizing pancreatitis.

Methods: Forty-seven male Wistar albino rats were randomized into seven experimental groups. In group I, animals were sham-operated (n = 5). In groups II, III, IV, IIepo, IIIepo, and IVepo, AP was induced by sodium taurodeoxycholate treatment (n = 7). In groups II, III, and IV, 1 ml normal saline and in groups IIepo, IIIepo, and IVepo, 1000 U/kg body weight erythropoietin (EPO) was administered intramuscularly immediately after the induction of AP. Animals were killed at 24, 48, and 72 h postoperatively. Histopathological and biochemical evaluations were performed.

Results: The serum levels of interleukin-6 (IL-6) and tissue levels of malondialdehyde were found to be significantly lower in EPO-administered groups when compared with the levels in groups without EPO treatment. The severity of pancreatic edema, acinar necrosis, inflammation, and perivascular infiltrate were reduced in all the EPO groups compared with the no-treatment groups.

Conclusions: Our findings may reflect the possible cytoprotective effect of EPO in acute necrotizing pancreatitis.
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http://dx.doi.org/10.1007/s00534-009-0082-xDOI Listing
October 2009

Treatment of severe amitriptyline intoxication with plasmapheresis.

J Clin Apher 2009 ;24(1):21-4

Department of Pediatric Neurology, Gazi University, Ankara, Turkey.

Tricyclic antidepressant poisoning is one of the most common causes of serious intoxication. Here, we report a 2-year-old girl with severe amitriptyline (70 mg/kg) intoxication. She was in comatose, had generalized tonic clonic seizure, ventricular tachycardia, and wide QRS complexes. Although she did not respond to classical therapies, very good clinical response to plasmapheresis was obtained and she developed no complications. Thus, plasmapheresis may be an effective treatment modality in poisoning with drugs, which bind to plasma proteins with high affinity.
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http://dx.doi.org/10.1002/jca.20185DOI Listing
April 2009

[Cryptococcus neoformans meningitis in a HIV negative miliary tuberculosis-suspected patient].

Mikrobiyol Bul 2008 Jul;42(3):519-24

Zonguldak Karaelmas Universitesi Tip Fakültesi, Enfeksiyon Hastaliklari ve Klinik Mikrobiyoloji Anabilim Dali, Zonguldak.

Cryptococcosis caused by Cryptococcus neoformans has a wide range of clinical presentations, varying from asymptomatic colonization of the respiratory airways to the dissemination of infection into different parts of body. It is more common among immunosupressed patients such as human immunodeficiency virus (HIV) positive ones. In this report we present a case with C. neoformans meningitis and miliary pulmonary infiltrates suggesting pulmonary tuberculosis without HIV infection. A-70-years-old male was admitted to the hospital with mental confusion, 3-weeks history of headache, weight loss, dry cough and fatigue. Physical examination was normal except neck stiffness. Cerebrospinal fluid (CSF) white cell count was 120/mm3 (80% polimorphonuclear cells). Gram staining of CSF revealed poorly stained gram-positive yeast cells. Empirical therapy with lipozomal amphotericin B, ceftriaxone and ampicillin combination was started. When C. neoformans growth was detected on CSF culture, ceftriaxone and ampicillin were discontinued. Patient became conscious at 24th hour of the treatment. Peripheric blood flow-cytometric analysis revealed a significant decrease in absolute CD4+ T lymphocytes, and in CD8+28+ T lymphocytes in addition a significant increase in natural killer cell ratio. Blood immunoglobulin and complement levels were found normal. Cranial magnetic resonance imaging and computerized tomogralphy (CT) of the abdomen were normal, however, chest CT revealed multiple parenchymal millimetric nodular infiltrations on both sides and minimal fibrotic alterations. Acid-fast staining of CSF, tuberculosis culture, tuberculosis PCR results and repeated HIV serology were found negative. Despite the lack of microbiological confirmation, empirical antituberculosis treatment was also started with the suspicion of miliary tuberculosis as the patient had a symptom of long-term dry cough, miliary infiltrations on chest CT, anergic tuberculin skin test and a history of pulmonary tuberculosis in childhood. After two weeks, amphotericin B was changed to oral fluconazole which was continued for an additional eight weeks. Antituberculosis therapy was given for nine months. Control chest CT taken after four months of antituberculosis therapy revealed improvement of the lesions. This presentation emphasizes the fact that cryptococcal infections may develop in HIV negative patients, even together with tuberculosis in certain cases and radiological findings of the two infections may be confusing when both of them invade the lungs.
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July 2008