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Histopathological changes in calcific aortic stenosis (CAS) resemble changes in coronary atherosclerosis. Concerning recent evidence on dietary and gut microbiota-related metabolites representing players in atherosclerosis, we aimed to investigate the link between dietary and gut microbiota-derived metabolites and CAS.We consecutively recruited eligible subjects with moderate-severe CAS (Prevalence of traditional cardiovascular risk factors or co-morbidities did not differ among groups (allWe found a significant association between choline levels and CAS presence and severity depicted on imaging modalities and histopathological examinations. Our study may open new horizons for prevention of CAS.

WOS: 000488637800004, PubMed: 31582678, Objective: Atrial structural remodeling has been suggested to contribute to atrial fibrillation (AF) recurrence following direct-current cardioversion (DCCV). The role of several inflammatory and extracellular matrix turnover markers in AF recurrence following DCCV has been investigated. However, data on the impact of galectin-3, which is known to play a role in various fibrotic conditions, including cardiac fibrosis are lacking. The aim of this study was to demonstrate the predictive role of serum galectin-3 levels in AF recurrence following successful DCCV. Methods: A total of 90 persistent AF patients who were scheduled for DCCV were prospectively enrolled. Serum samples were assayed to determine pre-DCCV galectin-3 levels using the enzyme-linked immunosorbent assay method. Patients were followed up for 3 months for AF recurrence. Results: Of 90 persistent AF patients (mean age: 55.33 +/- 7.94 years; 53.33% male) who underwent successful DCCV, 28 (31.11%) experienced early AF recurrence within 3 months. Patients with AF recurrence had a greater left atrial volume index (LAVI) (33.35 +/- 2.45 mL/m(2) vs. 29.21 +/- 3.08 mL/m(2); p, Hacettepe University Scientific Research Projects Coordination UnitHacettepe University [1993], This project was funded by Hacettepe University Scientific Research Projects Coordination Unit (project number: 1993).

WOS: 000482646600008, PubMed: 31375653, Objective: A well-developed coronary collateral circulation lowers both in-hospital and long-term morbidity and mortality limiting the infarct. Angiogenin (AGN) and osteopontin (OPN) are known to be potent inducers of angiogenesis. The aim of the present study was to investigate the relationship between serum ANG and OPN levels and collateral filling grade in subjects with stable coronary artery disease (SCAD). Methods: A total of 122 age- and gender-matched consecutive patients who were found to have total occlusion (n=70) and no significant stenosis in epicardial coronary arteries (n=52) who underwent coronary angiography due to SCAD between January 2015 and July 2017 were included in the study. AGN and OPN levels were measured using enzyme-linked immunosorbent assay. Coronary collateral circulation was graded using Rentrop's classification of collateral filling. Results: A total of 52 patients (61.60 +/- 11.78 years, 61.5% male) without significant epicardial coronary artery stenosis and 70 patients (62.87 +/- 8.24 years, 65.7% male) with totally occluded coronary arteries were included in the study. Subjects with total occlusion had significantly higher levels of AGN [122.00 (79.00-623.00) pg/mL vs. 98.00 (18.00-160.00) pg/mL, p, Hacettepe University Scientific Research Projects Coordination UnitHacettepe University [845], This research was supported by Hacettepe University Scientific Research Projects Coordination Unit (project no.: 845).

Beta‐trace protein (BTP) has emerged as a novel biomarker of cardiovascular risk. In this study, the authors aimed to assess the relationship between BTP levels and presence of atrial fibrillation in patients who had controlled hypertension (HTN) and normal renal function. A total of 80 controlled HTN patients with paroxysmal atrial fibrillation (PAF) and 80 age‐ and sex‐matched controls with controlled HTN were enrolled. Serum BTP levels were measured by enzyme‐linked immunosorbent assay. BTP levels were found to be significantly higher in patients with PAF (P

Cardiac Autoantibodies and AF Recurrence Introduction Recent evidence has suggested that autoantibodies may play an important role in the development of atrial fibrillation (AF). The predictive value of preprocedural autoantibodies against beta-1 adrenergic receptor (anti-β1-R) and M2-muscarinic acetylcholine receptor (anti-M2-R) for AF recurrence following cryoballoon-based pulmonary vein isolation (PVI) is still unclear. We aimed to determine the predictive value of preprocedural anti-β1-R and anti-M2-R levels for AF recurrence. Methods Eighty patients (mean age 54.25 ± 7.70 years; 40% female) with paroxysmal AF and preserved left ventricular function who underwent cryoballoon-based PVI were included in the study. Preprocedural anti-M2-R and anti-β1-R levels were measured with ELISA. Results At 1-year follow-up after ablation, late AF recurrence was observed in 17 (21.25%) patients. In the Cox regression model, including number of antiarrhythmic drugs, early AF recurrence, anti-β1-R levels >159.88 ng/mL, anti-M2-R levels >277.65 ng/mL, AF duration, and left atrial volume index, only anti-β1-R levels >159.88 ng/mL (HR: 4.281, P = 0.039) and anti-M2-R levels >277.65 ng/mL (HR: 4.313, P = 0.030) were found to be independent predictors of late AF recurrence. Anti-β1-R level >159.88 ng/mL was shown to predict late AF recurrence with a sensitivity of 70.59% and specificity of 90.48%. A cut-off value of 277.65 ng/mL for anti-M2-R level predicted AF recurrence with a sensitivity of 70.59% and specificity of 95.24%. Conclusion Preprocedural serum anti-β1-R and anti-M2-R levels are independent predictors of late AF recurrence following cryoballoon-based PVI in paroxysmal AF patients. Detection of preprocedural anti-β1-R and anti-M2-R levels may serve as a novel method for determination of paroxysmal AF patients who may not benefit from cryoballoon-based PVI.

Galectin-3 and Left Atrial Remodeling in AF Introduction Left atrial (LA) interstitial fibrosis is known to have a role in the initiation and maintenance of atrial fibrillation (AF). The role of galectin-3 in the pathogenesis of cardiac fibrosis has been demonstrated in previous studies. We aimed to determine whether serum galectin-3 level is associated with markers of atrial remodeling, including the extent of LA fibrosis detected by delayed enhancement magnetic resonance imaging (DE-MRI) and atrial electromechanical delay (AEMD) in paroxysmal AF patients with preserved left ventricular (LV) functions. Methods and Results Thirty-three patients (58 [28–74] years, 51.5% male) with paroxysmal AF who underwent DE-MRI prior to cryoballoon-based AF ablation were included in the study. Serum galectin-3 levels were measured with ELISA. LA volume index (B ± SE: 0.424 ± 0.504, 95% CI: 0.560–2.627, P = 0.004) and serum galectin-3 levels (B ± SE: 0.549 ± 7.745, 95% CI: 16.874–47.550, P < 0.001) were found to be independently correlated with extent of LA fibrosis detected with DE-MRI in paroxysmal AF patients with preserved LV function. Correlation analysis between AEMD parameters and baseline characteristics showed that galectin-3 was significantly correlated with intra-left (ρ = 0.432, P = 0.012) and inter-AEMD (ρ = 0.395, P = 0.023). Duration of AF, LAD, and extent of LA fibrosis were also found to be significantly correlated with AEMD parameters. Conclusion This is a hypothesis-generating study pointing out that serum galectin-3 level is significantly associated with atrial remodeling in paroxysmal AF patients with preserved LV function. Further studies are necessary to provide exact pathophysiological mechanisms.

Background Atrial fibrillation(AF) is the most common sustained arrhythmia. Its most feared sequelae are stroke and peripheral thromboembolism due to atrial thrombi formation. Mechanisms underlying the relationship between platelet activation and left atrial thrombi have not been clearly elucidated yet. We aimed to investigate whether immune-mediated platelet activation occurred in AF patients in this cross-sectional study. Methods Persistent and paroxysmal AF patients who underwent cryoballoon-based AF ablation between March 2015 and July 2016 were included as the patient group. Patients without AF in whom transseptal puncture was performed at the same period for purposes other than AF ablation were included as the control group. Peripheral and left atrial blood samples were obtained for determination of platelet Toll-like receptor(TLR)-2, TLR-4 and high mobility group box-1(HMGB-1) expression levels. Results A total of 75 subjects (53 patients with AF and 22 control subjects) [mean: 60.33 (SD: 6.14) years, 57.33% male] were included. Left atrial and peripheral TLR-2, 4 and HMGB-1 expression levels were significantly higher in the patient group when compared to the controls. Left atrial platelet TLR-2 and TLR-4 expression and serum HMGB-1 levels were higher in persistent AF patients compared to paroxysmal AF patients. In the patient group, left atrial expression of TLR-2, 4 and HMGB-1 were significantly higher than the peripheral expression levels. Conclusion Findings of our study suggest evidence for immune-mediated platelet activation in the left atria of AF patients.

WOS: 000416049100009, PubMed: 28295609, BackgroundLeft atrial appendage flow velocity (LAAFV) and presence of spontaneous echo contrast (SEC) have been reported to be predictors of thromboembolism in atrial fibrillation (AF) patients. Galectin-3 is a biomarker reflecting pro-inflammatory status, whose role in AF has recently drawn attention, particularly in persistent AF population. AimIn this study we aimed to investigate the association between serum galectin-3 levels and echocardiographic predictors of thromboembolism in persistent AF patients. MethodsWe included 65 persistent AF patients (55.5010.67years, 46.15% male). Transesophageal echocardiography (TEE) was performed to assess LAAFV and presence of left atrial (LA)/LA appendage (LAA)-located SEC and thrombus prior to direct current cardioversion or catheter ablation for AF. ResultsMedian galectin-3 level was 0.63ng/mL. Serum galectin-3 levels were significantly correlated with LAAFV (r=-.440, P, Hacettepe University Scientific Research Projects Coordination UnitHacettepe University [1993], This research was supported by Hacettepe University Scientific Research Projects Coordination Unit (project number: 1993).

Pathophysiologic mechanisms underlying lone atrial fibrillation (AF) have not been clearly demonstrated yet. Emerging evidence has indicated that autoimmunity may play a role in the development of AF. Relationship between serum anti-M2-muscarinic receptor autoantibody (anti-M2-R) and anti-β1-adrenergic receptor autoantibody (anti-β1-R) levels and lone paroxysmal atrial fibrillation (PAF) has not been investigated. We aimed to compare anti-M2-R and anti-β1-R levels between lone PAF patients and healthy control subjects. 75 patients with lone PAF (age: 52.80 ± 6.80 years, 53 % male) and 75 healthy control subjects (age: 53.30 ± 6.80 years, 54 % male) were enrolled in the study. Serum anti-M2-R and anti-β1-R levels were measured by ELISA and compared between two groups. Anti-M2-R [142.30 (77.65–400.00) vs. 69.00 (39.48–299.04) ng/mL; p

Atrial fibrillation(AF) is the most common sustained arrhythmia. One of its most feared sequelae is stroke and peripheral thromboembolism due to the formation of atrial thrombi. Mechanisms underlying the relationship between platelet activation and left atrial thrombi have not been clearly

The extracellular matrix plays a critical role in macrophage maturation. In this study, the HL60 cell line was used as a model of leukemic myeloid cell differentiation. We assessed the ability of HL60 cells cultured on fibronectin substratum prior to phorbol 12-myristate 13-acetate (PMA) induction to differentiate into terminally differentiated macrophages. Beside their distinctive macrophage morphology, they expressed antigen receptors CD14, TLR2, TLR4 and CD68, and displayed enhanced phagocytic activity and production of reactive oxygen species. Expression of CD13, CD33, CD15 and alpha-naphthyl-acetate esterase was also maintained, however, differentiated HL60 cells were HLA-DR and CD1a negative. Here, we describe the enhanced capacity of fibronectin-adherent HL60 cells to differentiate into macrophages in response to PMA.

Atrial fibrillation (AF) is the most common sustained arrhythmia. Inflammation has been suggested to play a vital role in the pathogenesis. Previous studies have investigated expression of inflammatory markers in AF. Several studies have focused on the effects of toll-like receptors (TLRs) on heart in terms of capability of modulating inflammation. In this study, we aimed to investigate whether peripheral monocyte TLR expression was associated with the AF presence, and recurrence of AF after cryoablation, as a reflection of inflammatory status. Patients with AF who were scheduled for cryoballoon-based ablation for AF and age- and gender-matched subjects in sinus rhythm were included. Peripheral monocyte TLR-2 and TLR-4 expressions were evaluated by flow cytometric analysis in peripheral venous blood samples obtained during evaluation in outpatient clinics: 172 patients (56.5 ± 6.6 years, 52.3% men) were included in the study. Peripheral monocyte TLR-2 and TLR-4 expression levels were significantly higher in patients with AF (p0.05). Among patients with AF, 12 patients (14.0%) developed AF recurrence at a follow- up of 17 months. Multivariate Cox regression analysis showed that left atrial volume index (hazard ratio 2.040, 95% CI 1.197 to 3.477, p = 0.009) and monocyte TLR-4 expression (hazard ratio 1.226, 95% CI 1.042 to 1.443, p = 0.014) were independent predictors of AF recurrence after blanking period following second-generation cryoballoon-based pulmonary vein isolation for paroxysmal AF. In conclusion, our study highlights the role of TLR-mediated inflammation in the pathogenesis of AF. This link may also constitute a therapeutic target in patients with AF.

Purpose Hemophagocytic lymphohistiocytosis (HLH) is a life-threatening condition characterized by uncontrolled inflammation and has common clinical and laboratory features with sepsis. The aim of this study was to investigate patients treated with severe sepsis who had bicytopenia for the presence of HLH. Materials and methods Patients with severe sepsis who were non-responsive to treatment and developed at least bicytopenia were included. Peripheral blood samples were collected and stored for later evaluation for natural killer (NK) activity and soluble interleukin-2 receptor levels. Diagnostic criteria of HLH were retrospectively analyzed. Results Seventy-five of 382 patients (20%) were followed as severe sepsis and septic shock. Among them, 40 patients had bicytopenia. Twenty-six of 40 patients were excluded due to the presence of active solid or hematological malignancies. Three patients died before fulfillment of HLH criteria and one patient denied to give consent. All of the remaining 10 patients had at least five of the eight criteria according to criteria of the Histiocyte Society. Only one of 10 patients was diagnosed as HLH and received treatment during intensive care unit stay. None of the 10 patients survived. Conclusions This study emphasizes to consider the possibility of HLH and the need of rapid assessment of patients with severe sepsis who had bicytopenia and were resistant to treatment in intensive care.

Evidence is accumulating that toll-like receptors (TLR) are involved in the initiation and progression of cardiovascular disease. Enhanced expression of these receptors on monocytes has been shown in patients with acute coronary syndrome (ACS). However, expression on platelets in this group of patients has not been evaluated yet. We aimed to demonstrate the possible relationship of platelet TLR-2 and TLR-4 expressions with stable coronary artery disease and ACS pathogenesis. In this observational case-control study, 40 patients diagnosed with ACS (unstable angina pectoris, non-ST-segment elevation and ST-segment elevation ACS), 40 patients diagnosed with stable coronary artery disease, and 40 age- and gender-matched subjects with normal coronary arteries were involved. Platelet TLR-2 and TLR-4 expressions were evaluated by flow cytometry in peripheral venous blood samples obtained before coronary angiography. A total of 120 patients (60.7 ± 12.3 years, 50% men) were included. Median platelet TLR-2 and TLR-4 expressions were greater in patients with ACS compared to those with stable angina pectoris and normal coronary arteries (29.5% vs 10.5% vs 3.0%, p0.001 and 40.5% vs 11.5% vs 3.0%, p0.001, respectively). Median platelet TLR-2 and TLR-4 expressions were also greater in patients with stable angina pectoris compared to those with normal coronary arteries (p0.05). In conclusion, this is the first study demonstrating enhanced TLR-2 and TLR-4 expressions on platelets in patients with ACS. These findings may suggest that platelet TLR expression as a novel potential prophylactic and therapeutic target in ACS.

There is emerging evidence that matrix metalloproteinases (MMPs) might be involved in blood brain barrier (BBB) breakdown in multiple sclerosis. A group of natural tissue inhibitors of metalloproteinases (TIMPS) regulates proteolytic activity to prevent tissue damage. TIMP-1 and MMP-9 are known to be secreted as heterodimers and TIMP-1 preferentially functions to inhibit MMP-9 activity. In this present study, the effects of IFNbeta-1a on serum MMP-9 and TIMP-1 were evaluated longitudinally during a one-year period. The MMP-9 levels showed no significant changes while TIMP-1 levels gradually and significantly increased during 3rd and 6th months of therapy compared with pretreatment levels.

Fluorouracil has been reported to induce severe side-effects in particular subjects who have deficiency in dehydropyrimidine dehyrogenase activity, the major enzyme in the catabolism of fluorouracil.In this study, we aimed to analyze the heterozygote and homozygote frequencies of dehydropyrimidine dehyrogenase gene mutation in 200 patients receiving fluorouracil based chemotherapy together with the assessment of the toxicity profile of these chemotherapy regimens.According to the results of clinical toxicity assessments, grade 3-4 hematologic toxicity was noted in 12% of the patients. Grade 3 gastrointestinal toxicity was present in 5% of the subjects with no grade 4 side effects. The heterozygote (2q(1-q)) and homozygote (q2) frequencies of dehydropyrimidine dehyrogenase gene mutation were calculated as 1.5% (3/200) and 0.000055% (1/18,043) in the analyzed samples.In this report, for the first time we documented the frequency of dehydropyrimidine dehydrogenase gene mutation in Turkish cancer patients. The determination of enzyme activity in suspected individuals and analysis of other mutations on a population basis would be the next steps for our country.

Introduction: Recent evidence have suggested that autoantibodies may play an important role in the development of atrial fibrillation (AF). Predictive value of pre-procedural autoantibodies against beta-1 adrenergic receptor (anti-β1-R) and M2-muscarinic acetylcholine receptor (anti-M2-R) for AF recurrence following cryoballoon-based pulmonary vein isolation (PVI) is still unclear. We aimed to determine the predictive value of pre-procedural anti-β1-R and anti-M2-R levels for AF recurrence in lone AF patients following cryoballoon-based PVI. METHODS: 80 patients (mean age 54.25±7.7 years; 40% males) with lone AF who underwent cryoballoon-based PVI were included in the study. Pre-procedural anti-M2-R and anti-β1-R levels were measured with ELISA. RESULTS: At one-year follow-up after ablation, late AF recurrence was observed in 17 (21.25%) patients. In the Cox regression model including number of antiarrhythmic drugs, early AF recurrence, anti-β1-R levels >159.88 ng/mL, anti-M2-R levels >277.65 ng/mL, AF duration and left atrial volume index; only anti-β1-R levels >159.88 ng/mL (HR: 4.281, p=0.039) and anti-M2-R levels >277.65 ng/mL (HR: 4.313, p=0.030) were found to be independent predictors of late AF recurrence. Anti-β1-R level >159.88 ng/mL was shown to predict late AF recurrence with a sensitivity of 70.59% and specificity of 90.48%. A cut-off value of 277.65 ng/mL for anti-M2-R level predicted AF recurrence with a sensitivity of 70.59% and specificity of 95.24%. CONCLUSION: Pre-procedural serum anti-β1-R and anti-M2-R levels are independent predictors of late AF recurrence following cryoballoon-based PVI in lone AF patients. Detection of pre-procedural anti-β1-R and anti-M2-R levels may serve as a novel method for determination of lone AF patients who may not benefit from cryoballoon-based PVI.

Galectin-3 is known to play an important role in a number of fibrotic conditions, including cardiac fibrosis. Many studies have focused on the association between galectin-3 levels and cardiac fibrosis in heart failure. However, the role of galectin-3 in the pathogenesis of atrial fibrillation (AF) has not been evaluated thoroughly yet. The aim of this study was to determine whether serum galectin-3 levels were elevated in patients with AF and preserved left ventricular function. Seventy-six patients with paroxysmal or persistent AF and preserved left ventricular systolic function and 75 age- and gender-matched control subjects were enrolled in this observational study. Galectin-3 levels were measured by enzyme-linked immunosorbent assay. Serum galectin-3 (median 0.6 ng/ml [interquartile range 0.2 to 1.4] vs 0.5 ng/ml [interquartile range 0.1 to 0.7], p0.001) and left atrial volume index (LAVI) (mean 29.5 ± 3.5 vs 26.5 ± 2.5 ml/m(2), p0.001) were significantly greater in patients with AF compared with the control group. Serum galectin-3 levels were also significantly higher in patients with persistent AF than those with paroxysmal AF (median 0.8 ng/ml [interquartile range 0.4 to 1.4] vs 0.5 ng/ml [interquartile range 0.2 to 0.9], p0.001). Multivariate regression analysis demonstrated that serum galectin-3 (odds ratio 87.53, 95% confidence interval 6.06 to 1,265.03, p = 0.001) and LAVI (odds ratio 1.38, 95% confidence interval 1.19 to 1.60, p0.001) were independent predictors of AF. Only LAVI was independently correlated with serum galectin-3 levels in patients with AF in linear regression analysis. In conclusion, serum galectin-3 is significantly elevated and is also significantly correlated with LAVI in patients with AF with preserved left ventricular function.

Aims Atrial fibrosis has been found to be associated with recurrent atrial fibrillation (AF) following catheter ablation. Autoantibodies against M2-muscarinic receptors (anti-M2-R) may play a role in the development of AF by inducing left atrial (LA) fibrosis. In this study, we aim to compare anti-M2-R levels between paroxysmal lone AF patients and healthy control subjects and to investigate the relationship between pre-ablation anti-M2-R level, LA fibrosis quantified by delayed enhancement magnetic resonance imaging (DE-MRI), and AF recurrence following cryoablation. Methods and results Thirty-one patients with paroxysmal lone AF (53.4 ± 8.0 years, 61% male), who underwent cryoballoon-based ablation, along with 31 healthy control subjects were included. Enzyme-linked immunosorbent assay tests to measure serum anti-M2-R levels were performed in both groups and DE-MRI was done to quantify LA fibrosis prior to the ablation in the patients. Anti-M2-R levels were higher in the study population when compared with control subjects [212.4 (103.2–655.5) vs. 73.0 (39.5–299.1) ng/mL, P < 0.001]. Anti-M2-R level predicted moderate-extensive LA fibrosis independent of other measures [odds ratio: 1.26 (95% confidence interval (CI): 1.04–1.53), P = 0.017]. At a mean follow-up of 35.2 ± 3.5 months, nine patients (29.0%) had AF recurrence. In the Cox regression model including pre-ablation anti-M2-R level, LA diameter, LA volume index, and moderate-extensive LA fibrosis, only moderate-extensive LA fibrosis predicted late AF recurrence independent of other measures [hazard ratio: 29.41 (95% CI: 3.52–250.00), P = 0.002]. Conclusion Serum anti-M2-R levels may be associated with the severity of LA fibrosis and may be implicated in the pathophysiology of AF recurrence following cryoablation. Detection of anti-M2-R levels may help select appropriate patients for the procedure.

Background: Recent studies have revealed a relationship between vitamin D deficiency and atherosclerosis. This study aims to investigate the impact of vitamin D deficiency and replacement on markers of subclinical atherosclerosis in young premenopausal women in whom vitamin D deficiency is prevalent. Methods: Thirty-one premenopausal vitamin D deficient women and 27 age and gender-matched control subjects were enrolled in this study. Markers of subclinical atherosclerosis including carotid intima-media thickness (cIMT), flow-mediated dilatation (FMD), endothelial progenitor cell (EPC) count and cytokine levels were determined at baseline. All measurements were repeated at 6-month follow-up in vitamin D-deficient subjects after vitamin D replacement. Results: Vitamin D deficient premenopausal women had lower FMD (9.9 ± 1.3 vs. 13.8 ± 1.7%, p < 0.001) and EPC counts at baseline. This population also had lower IL-10 and higher IL-17 levels. A 6-month vitamin D replacement therapy resulted in a significant increase in FMD (9.9 ± 1.3 vs. 11.4 ± 1.4%, p < 0.001) and EPC counts. Furthermore, cytokine profile shifted toward a more anti-inflammatory phenotype including elevated IL-10 and decreased IL-17 levels. cIMT was not different between patient and control groups and did not change following vitamin D replacement. Change in 25(OH)D and IL-17 levels were independent predictors of the change in FMD measurements following vitamin D replacement. Conclusion: This study demonstrates that endothelial function is impaired in otherwise healthy vitamin D deficient young premenopausal women and improves with 6-month replacement therapy. Immune-modulatory effects of vitamin D may, at least partly, be responsible for its beneficial effects on vascular health.

The aim of this study was to comparatively investigate the effects of 5-azacytidine-C (5-Aza), trichostatin-A (TSA), and all-trans retinoic acid (ATRA) on the mRNA expressions of the sodium and iodine (Na/I) symporter (NIS), thyroglobulin (Tg), thyroid peroxidase (TPO), and the thyroid-stimulating hormone receptor (TSH-R), as well as radioiodine (RAI) uptake in cancer (B-CPAP) and normal (Nthy-ori 3-1) thyroid cell lines. Cell lines were treated with 10 ng/mL of TSA, 5 μM of 5-AZA, and 1 μM of ATRA, according to the MTT (methyl-thiazol-tetrazolium) test results. Additionally, recombinant thyroid-stimulating hormone (rTSH) was also applied, with a selected dose of 100 ng/mL. Following the treatment, NIS, Tg, TPO, and TSH-R mRNA levels were detected by real-time-polymerase chain reaction (RT-PCR) and RAI uptakes were measured by using a well counter as counts/cell number. 5-Aza increased TSH-R mRNA expression in both of the cell lines and decreased TPO, NIS, and Tg mRNA levels in the cancer cell line. In the normal thyroid cell line, 5-AZA increased TPO mRNA levels by 2-fold and made no differences in NIS and Tg mRNA levels. TSA treatment repressed NIS and Tg mRNA levels and made no change on other thyroid-specific genes that were investigated in the cancer cell line. In the normal thyroid cell line, TSA increased TSH-R mRNA levels in 72 hours and created no important difference in the other genes. ATRA repressed the TSH-R mRNA levels in the normal thyroid cell line and increased the TPO and Tg mRNA levels slightly in both the cell lines. Furthermore, in short-term treatment, ATRA repressed the NIS gene expression slightly, but in the long term, this repression turned to basal levels. 5-Aza, TSA, and ATRA did not make any changes in RAI uptake in the cancer cell line, but rTSH increased RAI uptake significantly. In the normal thyroid cell line, TSA and ATRA decreased RAI uptake (to 1/10 and 1/2, respectively), but 5-Aza and rTSH increased RAI uptake significantly (2- and 4-fold, respectively). In our study, we showed an increase in TSH-R gene expression and radioiodine uptake with 5-Aza. Further in vitro and in vivo studies are needed to support our findings and the potential clinical use of this agent. © Mary Ann Liebert, Inc.

The widespread use of chemotherapy in the treatment of cancer has led to anxiety about the possible hazards to staff involved in the preparation and administration of cytotoxic agents. Careless handling of antineoplastic drugs may lead to exposure in detectable amounts by means of chemical or biological methods in the body fluids or cell samples but the information about the mutagenic effects of these agents on nurses is limited and inconsistent. DNA damage in peripheral lymphocytes of 30 professional nurses employed in the oncology departments for at least 6 months were examined by the alkaline single cell gel electrophoresis, 'COMET' technique. The results were compared to that of 30 controls with comparable age, sex and smoking habits, not practising in the chemotherapy services. Work characteristics of the exposed nurses and the use of personal protective equipment were also investigated. The DNA damage observed in the lymphocytes of the nurses was significantly higher than the controls (p0.001). The observed DNA damage was found to be significantly lower (p0.001) in nurses applying the necessary individual safety protections during their work. Cigarette smoking was not related to increases in DNA damage, also a significant association was not found between the duration of occupational exposure to antineoplastic drugs and the DNA damage.

Background The hereditary hemochromatosis gene HFE plays a pivotal role in iron homeostasis. The association between cancer and HFE hetero- or homozygosity has previously been shown including hepatocellular and nonhepatocellular malignancies. This study was performed to compare frequencies of HFE C282Y and H63D variants in Turkish women with breast cancer and healthy controls. Methods Archived DNA samples of Hacettepe University Oncology Institute were used in this study. The HFE gene was investigated by PCR-RFLP. Results All subjects studied were free from C282Y mutation. Thirty-nine patients had H63D mutation and were all heterozygous. H63D allele frequency was 22.2% (39/176) in the breast cancer patients, and 14% (28/200) in the healthy volunteers. Statistical analysis of cases with HFE H63D phenotype showed significant difference between breast cancer and healthy volunteers (P = 0.02). Conclusion Our results suggest that HFE H63D mutation frequencies were increased in the breast cancer patients in comparison to those in the general population. Also, odds ratios (odds ratio = 2.05) computed in this study suggest that H63D has a positive association with breast cancer.

Electrical cardioversion (EC) is one of the most effective treatment modalities in restoration of sinus rhythm (SR) in atrial fibrillation (AF) patients. Atrial structural remodeling has been suggested to contribute to AF recurrence following EC. Role of several inflammatory and extracellular matrix