Palladium Metal Nanocomposites Based on PEI-Functionalized Nitrogen-Doped Graphene Quantum Dots: Synthesis, Characterization, Density Functional Theory Modeling, and Cell Cycle Arrest Effects on Human Ovarian Cancer Cells.

In this study, the synthesis, characterization, density functional theory calculations (DFT), and effect of polyethylenimine (PEI)-functionalized nitrogen-doped graphene quantum dots (PEI N-GQDs) and their palladium metal nanoparticles nanocomposites (PdNPs/PEI N-GQDs) on cancer cells were extensively investigated. The focus also includes investigating their cytotoxic and apoptotic effects on ovarian cancer cells, which pose a serious risk to women's health and have high death rates from delayed diagnosis, inadequate response to treatment, and decreased survival. Graphene quantum dots and their palladium nanocomposites were differentially effective against ovarian cancer cell lines. In particular, the smaller particle size and morphology of PdNPs/PEI N-GQDs nanocomposites compared with PEI N-GQDs probably enhance their activity through highly improved uptake by cells. These findings emphasize the importance of particle size in composite drugs for efficient cancer treatment. DFT results revealed that the Pd-containing nanocomposite, with a smaller highest occupied molecular orbital-lowest unoccupied molecular orbital gap, exhibited higher reactivity and anticancer effects in human ovarian cancer cell line, OVCAR-3. Significantly, the application of nanocomposites to ovarian cancer cells initiated apoptosis, offering valuable insights into the intricate interplay between nanomaterials and cancer biology.

Comparative Metabolomic Profiles of Vascular Involvement in Behçet's Disease.

BACKGROUND: Behçet's disease is a systemic, inflammatory disease affecting multiple organs. Vascular involvement is the main cause of morbidity and mortality in Behçet's disease patients. Though clinically well-defined, there is limited information related to disease pathogenesis and vascular incidence in this patient group. The aim of this study is to investigate the unique metabolic signatures of Behçet's disease patients with vascular involvement. METHODS: Metabolomic profiling was performed on serum samples of 48 Behçet's disease patients (18 with vascular involvement) and 40 healthy controls using gas chromatography-mass spectrometrybased untargeted metabolomics analysis. Multivariate and univariate statistical analyses were performed to find altered metabolites and pathways. RESULTS: Untargeted metabolomics results showed that a total of 168 metabolites were identified. The comparison between the groups of Behçet's disease, vascular involvement in Behçet's disease, and the healthy control group showed that altered amino acid and oxidative stress pathways, especially with glutathione synthesis, could be an important stage for developing Behçet's disease. CONCLUSION: In the present work, the untargeted metabolomics approach provided new molecular insights for a better understanding of Behçet's disease pathogenesis and also developing vascular involvement in Behçet's disease at the metabolite level. The results showed that vascular involvement in Behçet's disease could be highly linked with amino acid metabolism and also the antioxidant system, and these disease-related pathways could be evaluated with further experiments for diagnosis and prognosis of Behçet's disease and also for vascular involvement in Behçet's disease.

Cytotoxic and Apoptotic Effects of the Combination of Borax (Sodium Tetraborate) and 5-Fluorouracil on DLD-1 Human Colorectal Adenocarcinoma Cell Line.

Objectives: Colorectal cancer (CRC) remains a crucial health problem due to the toxicity of 5-Fluorouracil (5-FU) as first-line chemotherapy agent for treating CRC. The anticancer effects of boron and its compounds have been shown in various cell lines. This study aimed to examine the cytotoxic and apoptotic effects of borax (sodium tetraborate) alone or along with 5-FU on human CRC cells, DLD-1. Materials and Methods: Cytotoxicity and apoptosis were determined by 3-(4,5-dimethylthiazolyl-2)-2,5-diphenyltetrazolium bromide (MTT) assay, 4',6-diamidino-2-phenylindole and annexin V/propidium iodide staining. Results: The results showed that combined treatment revealed a significant time- and concentration-dependent cytotoxic effect on DLD-1 cells compared with borax or 5-FU treatment alone. The combination of borax and 5-FU induced a clear increase in the early apoptotic cell percentage, compared to the cells treated with monotherapies. Additionally, a significant increase in condensed and fragmented nuclei was detected in DLD-1 cells treated with the combination treatment compared with borax or 5-FU alone. Conclusion: Our current findings suggest that the combination of borax with 5-FU has a strong cytotoxic and apoptotic effect on the human CRC DLD-1 cells.

The role of IL-6 and osteoprotegerin in bone metabolism in patients with Graves' disease.

BACKGROUND: Increased bone turnover is a hallmark of hyperthyroidism. The underlying factors of how thyroid hormones affect bone cells are still under the spotlight. Previous studies indicated serum osteoprotegerin (OPG), receptor activator of NF-kB ligand (RANKL), and interleukin-6 (IL-6) as mediators of the effect of thyroid hormones on bone metabolism. Ultimately, the present research aimed to examine the association of IL-6 with OPG and RANKL in patients with hyperthyroidism. METHODS: We carried out this study with 39 newly diagnosed and untreated Graves' patients and 43 healthy controls. In addition to routine tests, we measured serum OPG, RANKL, and IL-6 levels. RESULTS: Mean age and sex distribution were similar in both groups. The hyperthyroid group had significantly higher OPG (p = 0.002) and IL-6 (p < 0.001) levels, but RANKL levels were significantly lower in this group (p < 0.001). We found OPG not to correlate with free T4 and T3, while it had a moderate and negative correlation with thyrotropin (TSH) (r = -0.372, p = 0.001). IL-6 had no correlation with OPG but positively correlated with free T4 (r = 0.445, p < 0.001) and free T3 (r = 0.326, p = 0.035). It also negatively correlated with RANKL (r = -0.247, p = 0.033). DISCUSSION: Maintaining skeletal development and integrity is partially regulated by a normal balance of thyroid hormones. We concluded that increases in serum OPG and IL-6 levels accompanied hyperthyroidism. However, excessive levels of the hormones might cause drops in serum RANKL levels. Our results suggested that OPG, RANKL, and IL-6 might be involved in the cross-talking among immunity, thyroid function, and bone metabolism in the case of hyperthyroidism.

Evaluation of erythrocyte membrane fatty-acid compositions in association with interleukin-6 levels in patients with COVID-19.

OBJECTIVE: The cytokine storm presented in the hyperimmune response is related to poor prognosis in people with COVID-19. Interleukin-6 (IL-6) is one of the most prominent cytokines, especially on mucosal surfaces during infection, causing the cytokine storm. Polyunsaturated fatty acids (PUFAs) are the precursors of eicosanoids, which play critical roles in immune regulation and inflammation. The balance between ω-3 and ω-6 levels in the cell membrane has a critical role in regulating the equilibrium between proinflammatory and antiinflammatory processes and inducing IL-6 production. The present study focused on inflammatory and antiinflammatory mechanisms in COVID-19 over PUFAs and on relating their levels with disease prognosis and severity. METHODS: A total of 106 participants were included in the study. They were divided into three groups according to IL-6 level- 1: <35 pg/mL, 2: between 35 and 300 pg/mL, and 3: >300 pg/mL. Erythrocyte membrane PUFA compositions were analyzed by group. RESULTS: Levels of γ-linolenic acid and ω-6/ω-3 ratios were significantly increased in all comparison groups (P < 0.05). Total ω-6 and the ratio of arachidonic acid to eicosopentaenoic acid showed a statistically significant difference only between groups 1 and 3 (P < 0.05). There was a moderately negative correlation between total ω-3 and IL-6 and procalcitonin. There were positive correlations with ω-6/ω-3 ratio inflammatory markers, and the total ω-6 index also showed a moderately positive correlation with IL-6, procalcitonin, and D-dimer levels. CONCLUSIONS: The ratio of arachidonic acid to eicosopentaenoic acid, and ω-3 PUFAs, can be systemic signs of poor prognosis, increased lung damage, and high mortality in COVID-19, together with IL-6.

Evaluation of the relationship of lymphangiogenesis markers with disease pathogenesis in patients with Behçet's uveitis.

OBJECTIVES: The present study aims to evaluate the relationship between Behçet's uveitis and lymphangiogenesis by determining levels of Vascular endothelial growth factor-C (VEGF-C, its receptors sVEGFR-2, sVEGFR-3 and lymphangiogenesis markers podoplanin (PDPN) and lymphatic vessel endothelial hyaluronan receptor 1(LYVE-1), and C-type lectin domain family 1 member B (CLEC2). MATERIALS AND METHODS: 55 patients with BD uveitis and 31 healthy control subjects were enrolled in the study. RESULTS: sVEGFR-2, sVEGFR-3, VEGF-C/sVEGFR-2 ratio, PDPN and LYVE-1 levels were higher in the patient group. A positive correlation was found between LYVE-1 and hsCRP levels. PDPN had a strong predictive value for progression with a cut-off value of 2 pg/mL, with 69% sensitivity and 68% specificity (p = 0.001). CONCLUSION: LYVE-1 and PDPN can be good representatives of the ongoing inflammatory processes in BD uveitis and point out that the disease can be related to lymphangiogenesis.

Determination of serum vascular endothelial growth factor (VEGF) and VEGF receptor levels with VEGF gene polymorphisms in patients with Behçet's uveitis.

BACKGROUND: Behçet's disease (BD) is a chronic inflammatory vasculitis affecting multiple organs. Uveitis is frequently seen in patients with BD, especially in Turkish population. OBJECTIVES: To investigate vascular endothelial growth factor (VEGF) gene polymorphisms along with the levels of VEGF and VEGF receptors in patients with Behçet's uveitis (BU). MATERIAL AND METHODS: Fifty-five BD-associated uveitis patients and 30 ageand sex-matched controls were included in this case-control study. The genotypes of the single nucleotide poymorphisms (SNPs): rs2010963 (+405G), rs3025039 (+936T) and rs699947 (-2598A) of the VEGF-A gene were determined using real-time polymerase chain reaction (RT-PCR) and serum levels of VEGF and VEGF receptors were measured using enzyme-linked immunosorbent assay (ELISA). RESULTS: No associations of the VEGF gene polymorphisms were observed in BD uveitis patients, but arthritis was present in 53.3% of patients not possessing CT genotype in C3025039→T polymorphism (p = 0.024). Although there were no statistically significant differences in serum VEGF-A, VEGF-C and soluble vascular endothelial growth factor receptor-3 (sVEGFR-3) levels (p < 0.05), serum vascular endothelial growth factor receptor-1 (VEGFR-1) and sVEGFR-3 levels were significantly higher in the BD group (p < 0.001 and p = 0.001, respectively). In addition, VEGF-C/soluble vascular endothelial growth factor receptor-2 (sVEGFR-2) ratio was significantly higher (p < 0.001), while VEGF-A/VEGFR-1 and VEGF-C/sVEGFR-3 ratios were significantly lower (p < 0.001 and p = 0.033, respectively) in BD patients compared to controls. Also, VEGF-C/sVEGFR-3 (p = 0.024, r = 0.37) and VEGF-C/sVEGFR-2 (p = 0.020, r = 0.38) ratios were positively correlated with disease duration. CONCLUSIONS: The significant changes in sVEGFR-3 levels and VEGF-C/sVEGFR-3 ratio has shown that lymphangiogenesis processes might take place in the pathogenesis of BD uveitis, and these parameters can be important indicators of evaluation of BD patients with uveitis together with disease duration.

Serum VEGF-A and VEGFR-1 levels in patients with adult immunoglobulin A vasculitis.

AIM: Immunoglobulin A vasculitis (IgAV) is classified as a leukocytoclastic vasculitis characterized by immune deposits in endothelial walls of small vessels causing vascular endothelial injury. The aim of the present study is to evaluate levels of vascular endothelial growth factor-A (VEGF-A) and VEGF receptor-1 (VEGFR-1) levels in adult IgAV patients. METHOD: Thirty-seven adult IgAV patients admitted to the Rheumatology Clinic meeting the IgAV American College of Rheumatology (ACR) criteria and 32 control subjects were enrolled in the study. Disease activity was categorized as "remission" or "active" according to Birmingham Vasculitis Activity Score (BVAS). Serum VEGF-A, VEGFR-1 levels and VEGFR-1/VEGF-A ratio were evaluated in patient and control groups. RESULTS: Serum median VEGF-A, VEGFR-1 and VEGFR-1/VEGF-A ratios were significantly higher in the patient group when compared to controls (235.9 [155-308.4] pg/mL vs. 78.8 [29.7-210.3] pg/mL, 400 [277.2-724.3] pg/mL vs. 31.5 [12.5-214.4] pg/mL and 1.85 [0.57-2.97] vs. 0.46 [0.38-0.63] respectively, all P values <.001). VEGFR-1 had the strongest predictive value with a cut-off value of 0.6 with 75% sensitivity and 73% specificity (P < .001). CONCLUSION: This study is the first report indicating elevated serum VEGF-A, VEGFR-1, and more importantly VEGFR-1/VEGF-A ratio can be good representatives of the inflammatory processes together with vascular endothelial injury in adult IgAV patients. VEGFR-1 seems to be a more important indicator of the ongoing inflammation.

The effects of a novel non-invasive application of platelet-rich fibrin on periodontal clinical parameters and gingival crevicular fluid transforming growth factor-ß and collagen-1 levels: A randomized, controlled, clinical study.

BACKGROUND: Several potential benefits have been attributed to the platelet-rich fibrin (PRF), including enhanced tissue healing properties. In this study, we hypothesized that the application of PRF as an adjunct to conventional scaling and root planing (ScRp) would enhance the outcomes of non-surgical periodontal therapy. METHODS: The present study was a split-mouth randomized controlled clinical trial design in 24 deep periodontal pockets in 12 patients with periodontitis. The pockets were randomly assigned as test or control. The test group received PRF as an adjunct to ScRp, whereas the control group received ScRp only. We measured periodontal clinical parameters at baseline, 3, and 6 months after the treatments. To study the initial healing in response to treatment, transforming growth factor-ß (TGF-ß) and collagen-1 (Col-1) in gingival crevicular fluid (GCF) were measured using enzyme-linked immunosorbent assay at baseline, third, seventh, and 14th days. RESULTS: The test group showed a significantly greater pocket reduction, higher clinical attachment gain, and less gingival recession than the control group at 3 and 6 months. The test Col-1 levels (1.27 ± 1.05, 1.35 ± 0.76, 0.97 ± 0.53 ng/site) and TGF-ß levels (11.93 ± 2.68, 12.54 ± 3.66, 17.19 ± 11.66 pg/site) were higher than the control Col-1 levels (0.76 ± 0.20, 0.84 ± 0.24, 0.57 ± 0.19 ng/site) and TGF-ß levels (6.34 ± 1.67, 6.35 ± 3.44, 7.51 ± 2.85 pg/site) at all measurement days respectively. CONCLUSIONS: Non-surgical application of the PRF as an adjunct to conventional ScRp may effectively improve the periodontal clinical parameters via increasing expression of the GCF TGF-ß and Col-1 levels.

Development and optimization of simultaneous determination of fat soluble vitamins by liquid chromatography tandem mass spectrometry.

OBJECTIVE: Fat-soluble vitamins (A, D, E and K) are isoprene derived apolar molecules. While deficiencies of these vitamins have been associated with various diseases such as type 2 diabetes and cancer, high doses of Vitamin A and D can cause toxic effects. Accurate detection of serum levels of these vitamins have critical importance. In this study, it is aimed to develop and validate a sensitive and specific Liquid Chromatography Tandem Mass Spectrometry (LC-MS / MS) method that allows simultaneous analysis of fat-soluble vitamins. MATERIALS AND METHODS: Serum samples were deproteinized with methanol and chromatographic separation of analytes were performed by LC-MS/MS system (Agilent Technologies 6420 Triple Quadrapole LC-MS), Agilent Pursuit PFP column (100 mm × 3.0 mm; 3.0 µm), in gradient mode using Mobile phase A (milli-Q+0.1 % formic acid) and Mobile phase B (Methanol+0.1 % formic acid). Ion scan was performed in MRM (multiple reaction monitoring) mode with positive ion selectivity in ESI ion source. RESULTS: The retention times were 6.93 min, 6.94 min and 9.34 min while concentrations were linear in the ranges between 10-150 ng/mL, 3-90 µg /dL and 6-90 µg/mL for 25-hydroxy vitamin D3 (25-OHD3), Vitamin A and Vitamin E, respectively. Inter-day Coefficient Variation (CV%) values for Vitamin A, Vitamin E and 25-OHD3 were; 9.08 %, 9.85 % and 3.07 % and intra-day CV% values were; 2.98 %, 5.05 % and 5.01 %. LOD and LOQ results were 2.11 µg/dL and 3.50 µg/dL for Vitamin A; 1.71 µg/mL and 2.45 µg/mL for Vitamin E; 1.47 ng/mL and 2.50 ng/mL for 25-OHD3, respectively. CONCLUSION: In this study, a LC-MS/MS method that can analyze fat soluble vitamins in 13 min was developed and validated. This method will be useful for clinical purposes by replacing low specificity immunoassay methods and High Performance Liquid Chromatography (HPLC) methods that can not allow simultaneous analysis.

Evaluation of atherogenic laboratory markers in Behçet's disease patients with vascular involvement.

INTRODUCTION: Behçet's disease is a chronic inflammatory vasculitis presenting with immunological and endothelial changes. The aim of the present study is to evaluate blood levels of diagnostic markers which can be used in Behçet's patients with vascular involvement. MATERIAL AND METHODS: Fifty Behçet's patients (22 with vascular involvement) and 30 healthy controls were included in the study. High-sensitivity C-reactive protein (hsCRP), erythrocyte sedimentation rate (ESR), tumor necrosis factor-α (TNF-α), apolipoprotein A1 (apoA1), apolipoprotein B (apoB), high-density lipoprotein (HDL), low-density lipoprotein (LDL), triglyceride, total cholesterol, Lp-plA-2, homocysteine and ischemia modified albumin (IMA) levels were analyzed. Statistical analysis was performed with the SPSS program version 11.0. p < 0.05 was accepted as statistically significant. RESULTS: hsCRP, TNF-α, homocysteine, IMA, apoA1, apoB, HDL, Lp-pla2 and ESR levels in patient and control groups were significantly different (p < 0.001, p = 0.001, p < 0.001, p < 0.001, p = 0.005, p < 0.001, p < 0.001, p < 0.001 and p = 0.003 respectively). In Behçet's patients with vascular involvement, homocysteine, TNF-α and Lp-pla2 levels were significantly higher than in Behçet's patients without vascular involvement (p = 0.035, p = 0.010 and p < 0.001 respectively). CONCLUSIONS: Increased levels of inflammatory and atherogenic markers in Behçet's patients are an expected outcome due to the inflammatory nature of the disease. Especially, elevated levels of homocysteine, TNF-α and Lp-pla2 make them candidate diagnostic tools to be helpful in clinical evaluation of Behçet's disease patients with vascular involvement.

Sesamin ameliorates mucosal tissue injury of mesenteric ischemia and reperfusion in an experimental rat model.

INTRODUCTION: Mesenteric ischemia/reperfusion (I/R) injury is a serious clinical condition. There were a lot of experimental studies performed in the treatment of I/R injury. To our knowledge, this is the first experimental study with effects of sesamin on I/R injury model. We aimed to investigate the protective effect of sesamin on mesenteric I/R injury model. MATERIAL AND METHODS: A total of 32 male Sprague-Dawley rats were divided into four groups. Control group: superior mesenteric artery (SMA) exposed without clamping. I/R group: SMA was clamped for 60 min and then reperfused for 2 h. Sesamin group (S): 30 mg/kg sesamin were given for 5 days, and SMA exposed without clamping. I/R + S group: 30 mg/kg sesamin were given for 5 days, SMA was clamped for 60 min, and then reperfused for 2 h. Plasma and tissue oxidant parameters were investigated as well as histopathological evaluation. RESULTS: Plasma and tissue total antioxidant status (TAS) levels were significantly higher in I/R + S group compared to the rest (p < 0.005). The plasma TAS levels in I/R group was significantly low. The highest tissue TAS levels were detected in I/R + S group. The high levels of plasma and tissue TOS were found in I/R + S group. Plasma and tissue OSI levels were significantly higher in I/R group. Histopathologic evaluation showed that the mean level of intestinal tissue injury score in I/R group was 2.75 and 1.38 in I/R + S group. CONCLUSIONS: Sesamin helps to protect the intestinal tissue at the cellular level by reducing the oxidative stress and inflammation at both the plasma and tissue levels in the experimental I/R model.

Serum neopterin and ischemia modified albumin levels are associated with the disease activity of adult immunoglobulin A vasculitis (Henoch-Schönlein purpura).

AIM: The aims of the study are to investigate serum neopterin and ischemia modified albumin (IMA) levels in patients with immunoglobulin A vasculitis (IgAV) and evaluate the association of these markers with disease activity and relapse. METHOD: Thirty-four consecutive adult patients (24 male and 10 female) admitted to the rheumatology clinic and met the IgAV American College of Rheumatology (ACR) criteria were enrolled in this cross-sectional study. Demographic and clinical features of IgAV and a control group were recorded into a predefined protocol. Disease activity was categorized as "remission" or "active" according to Birmingham Vasculitis Activity Score (BVAS). BVAS ≥ 1 was accepted as "active". Serum neopterin levels, high-sensitivity C-reactive protein (hsCRP) and IMA were evaluated according to BVAS and compared to the healthy control group. RESULTS: Serum median (interquartile range) neopterin, IMA levels and hsCRP were higher in the study group than in control group (2.01 [12.5] ng/mL vs 1.77 [1.37] ng/mL, 0.67 [0.2] ng/mL vs. 0.43 [0.17] ng/mL, 5.6 [17.1] mg/L vs. 1.55 [1.6] mg/L, P = .095, P < .001 and P = .002, respectively). When evaluated according to BVAS, IMA and hsCRP levels were significantly higher in the group with active disease (0.77 [0.12] vs 0.61 [0.13] and 14.85 [4.6], P = .009 and P = .03, respectively). Serum neopterin levels were significantly higher in the active group compared to BVAS (18.95 [32.36] vs 1.63 [1.48], P < .001). CONCLUSION: Oxidative stress is important in IgAV pathogenesis. Roles of hsCRP, neopterin and IMA as potential markers of diagnosis and disease activity seem to be worth studying in future studies with larger study groups.

Calculation of Biological Variation Components and Reference Change Value for Serum Copper and Zinc.

BACKGROUND: Zinc and copper are among the most important trace elements. Deficiencies of these trace elements cause a wide variety of disorders. The present study aims to report the definitive assessment of biological variation (BV) parameters for these elements as within-subject BV (CVI), between subject BV (CVG), index of individuality (II), and reference change value (RCV) in a Turkish cohort study group. METHODS: Ten blood specimens were collected weekly from 20 healthy volunteers (13 women, 7 men) for 10 weeks. Collected sera were stored at -80°C until the time of analysis. Serum zinc and copper levels were analyzed with atomic absorption spectrometry and ANOVA test was used to calculate the variations. RESULTS: The CVI and CVG for zinc were 6.26% and 23.27%, respectively. Analytical variation (CVA) was calculated as 4.24%. II and RCV for zinc were calculated as 0.26 and 21.51%, respectively. The CVI and CVG for copper were 6.05% and 19.64%, respectively. CVA was calculated as 4.24%. II and RCV for copper were calculated as 0.31 and 20.47%, respectively. CONCLUSIONS: Since II values were less than 0.6 for both analytes, the reference values will be of little use. RCV might be preferred for better evaluation instead.

Angiostatin levels in diabetes mellitus patients receiving insulin treatment: associations with laboratory findings, comorbidities, and medications

Background/aim: The clinical effect of angiostatin in diabetes mellitus (DM) patients receiving insulin is a meaningful gap in the literature. In this study, we aimed to show the levels and the clinical significance of angiostatin in DM patients receiving insulin. Materials and methods: This is a case-control study. Serum angiostatin levels were determined by ELISA. A total of 83 people consisting of healthy subjects (n = 36) and patients with a diagnosis of DM receiving insulin therapy (n = 47) were included in this study. Results: The mean angiostatin levels of the DM group were significantly higher than those of the control group (86.0 ± 68.1 ng/mL and 58.0 ± 22.4 ng/mL, respectively; P = 0.011). Significantly lower angiostatin levels were determined in the DM patients receiving metformin with respect to those not receiving metformin (97.2 ± 74.4 ng/mL and 49.3 ± 7.0 ng/mL, respectively; P = 0.021). Significantly higher levels of angiostatin were observed among the DM patients using a beta-blocker (BB) than the DM patients not using a BB (115.5 ± 78.71 ng/mL and 73.44 ± 60.08 ng/mL, respectively; p = 0.029). Conclusion: This is the first study evaluating and demonstrating the serum angiostatin levels in DM patients receiving insulin. Further studies are required to understand the effect of angiostatin in diabetics and the effect of medications on angiogenesis in these patients.

Evaluation of the effects of different treatment modalities on angiogenesis in heart failure patients with reduced/mid-range ejection fraction via VEGF and sVEGFR-1.

OBJECTIVES: To investigate the clinical significance of VEGF, sVEGFR-1 in heart failure reduced ejection fraction (HFrEF) and heart failure mid-range ejection fraction (HFmrEF) patients. Methods: A total of 104 people consisting of HFrEF and HFmrEF patients (n=54) and healthy (n=50) subjects were included in this comparative cross-sectional study. The study took place in Gulhane Training and Research Hospital, Ankara, Turkey, between  2011 and 2013. Serum VEGF, sVEGFR-1, plasma pro-BNP analysis and transthoracic echocardiography were performed.  Results: The average sVEGFR-1 level of the HFrEF and HFmrEF patients was significantly higher than the control group (0.185±0.122; 0.141±0.120; p=0.013). The average sVEGFR-1 level of the HFrEF and HFmrEF patients using beta-blocker was significantly higher than the HFrEF and HFmrEF patients not using it (p=0.015). There was a significant and positive correlation between sVEGFR-1 and N-terminal pro-brain natriuretic peptide (pro-BNP)  levels in the group with HF (r=0.211, p=0.044). Conclusion: It increases awareness about the role of sVEGFR-1 in HFrEF anf HFmrEF patients and the need for further studies. Beta-blocker may have a negative effect on angiogenesis in HFrEF and HFmrEF via increasing sVEGFR-1 levels. Additionally, Pro-BNP may contribute to inhibiting angiogenesis by increasing sVEGFR-1 levels and sVEGFR-1 may be an important biomarker in HFrEF and HFmrEF.

Effect of seasonal changes on nutritional status and biochemical parameters in Turkish older adults.

BACKGROUND/OBJECTIVES: Available data suggest that seasonal changes may influence the nutritional status and overall health of elderly individuals. Therefore, this study was conducted to investigate the effects of seasonal changes and related factors on energy and nutrient intake of older adults. SUBJECTS/METHODS: Individuals aged 65 years or over were prospectively enrolled in this single-center study (male: 11, female: 20). Data were collected between May 2013 and February 2014 during winter, spring, summer and autumn. Food consumption and biochemical parameters were taken during each season to assess the seasonal nutrition status of the elderly. Upon analysis of biochemical parameters (retinol, vitamin D and vitamin C), an high-performance liquid chromatography device was utilized whereas an Immulite 2000 device was utilized during analysis of serum folic acid and parathyroid hormone. RESULTS: Fruit, fat, egg and bread consumption varied seasonally in males and females (P < 0.05). During winter, daily energy intake was found to be greater than in other seasons in males (557 kcal) and females (330 kcal) (P < 0.05). Additionally, carbohydrates, vegetable protein, n-3 fatty acid and sodium intake increased in winter, while the n-6/n-3 ratio increased in summer among males (P < 0.05). Dietary fiber and sodium intake in winter, vitamin C, iron and zinc intake in spring, and cholesterol, retinol, vitamin D and niacin intake in autumn were found to be higher in females when compared to other seasons (P < 0.05). Serum parathyroid hormone level was higher in winter, and vitamin D level was higher in autumn in both genders (P < 0.05). In males, blood folic acid level was higher in winter, while vitamin C level was higher in females, and there was no seasonal variation in retinol concentration (P < 0.05). CONCLUSION: Food consumption and biochemical parameters showed significant seasonal variations in older adults. It is not clear if nutrition plans in older adults will benefit from consideration of seasonal changes in eating habits.

The relationship of serum VEGF and sVEGFR-1 levels with vascular involvement in patients with Behçet's disease.

Behçet's disease (BD) is a rare, chronic, inflammatory disorder characterized by multisystemic vasculitis including mucocutaneous, neurologic, and ophthalmic involvement. Our aim is to compare vascular endothelial growth factor (VEGF) and soluble vascular endothelial growth factor receptor-1 (sVEGFR-1) levels in BD, among the patients having or not having organ involvement, disease activation and especially vascular involvement. Fifty-five patients with BD, 25 of which were accompanied by vascular involvement, and 31 control subjects were included in the study. Disease activity was assessed with the Turkish version of Behçet Disease Current Activity Form (BDCAF) and active vasculitis lesions at the time of study were recorded. Age at diagnosis was 32.2 ± 4.6, while the mean duration of BD was 96.3 (72.3) months. The median for BDCAF score was 2.0 (range 0, 3.0), and 29 (52%) of patients had active BD. The serum VEGF and sVEGFR-1 levels in patients with BD were significantly higher than that in controls [(298 (338.5) pg/mL; 93 (93.5) pg/mL in patients and 136.2 (73) pg/mL; 56.5 (48.5) pg/mL in controls, respectively, p < .001 for both values] while difference in VEGF/sVEGFR-1 ratio was obtained close to borderline of significance (p = .03). Our study is the first report indicating elevated serum VEGF, sVEGFR-1, and more importantly VEGF/sVEGFR-1 ratio could play an important role in the development of trombosis in BD. VEGF and/or sVEGFR-1 should not be evaluated independently in the same patient group and the ratio of these two parameters is a more important indicator, especially in the evaluation of BD especially with vascular involvement together with the duration of disease.

Vascular endothelial growth factor and soluble vascular endothelial growth factor receptor-1 in patients with end-stage renal disease. Associations with laboratory findings, comorbidities, and medications.

OBJECTIVES: To show the levels of vascular endothelial growth factor (VEGF), soluble vascular endothelial growth factor receptor-1 (sVEGFR-1) in patients with end-stage renal disease (ESRD) and to show the associations with clinical findings such as demographic features, laboratory findings, comorbidities, and medications. METHODS: A total of 73 people, consisting of patients with ESRD (n=38) and healthy subjects (n=35) in Gulhane Education and Research Hospital, Ankara, Turkey, were included in this cross-sectional study between the years 2011 and 2013. Blood samples were obtained and plasma VEGF, sVEGFR-1 analyzes were performed. Results: The VEGF level of ESRD group was not significantly higher (0.280±0.264) than the control group (0.321±0.210) (p=0.475). The sVEGFR-1 level of ESRD group was significantly higher (0.217±0.135) than the control group (0.068±0.047) (p less than 0.001). The correlation between VEGF and sVEGFR-1 was significant and negative (r=-0.246, p=0.036). Average VEGF level of ESRD patients using recombinant human erythropoietin (rhEPO) was significantly higher (0.567±0.28) than the ESRD patients not using rhEPO (0.246±0.24) (p=0.025). CONCLUSION: Our study is the first showing the significance of sVEGFR-1 in ESRD patients, and associations with comorbidities, medications. Especially our finding of rhEPO and VEGF may illuminate a reasonable positive effect of rhEPO on angiogenesis. Soluble vascular endothelial growth factor receptor-1 and VEGF may be important markers in the pathophysiology of ESRD.

Bringing Packed Red Blood Cells to the Point of Combat Injury: Are We There Yet?

Objective: Hemorrhage is the leading cause of injury-related prehospital mortality. We investigated worst-case scenarios and possible requirements of the Turkish military. As we plan to use blood resources during casualty transport, the impact of transport-related mechanical stress on packed red blood cells (PRBCs) was analyzed. Materials and Methods: The in vitro experiment was performed in the environmental test laboratories of ASELSAN®. Operational vibrations of potential casualty transport mediums such as Sikorsky helicopters, Kirpi® armored vehicles, and the NATO vibration standard MIL-STD-810G software program were recorded. The most powerful mechanical stress, which was created by the NATO standard, was applied to 15 units of fresh (≤7 days) and 10 units of old (>7 days) PRBCs in a blood cooler box. The vibrations were simulated with a TDS v895 Medium-Force Shaker Device. On-site blood samples were analyzed at 0, 6, and 24 h for biochemical and biomechanical analyses. Results: The mean (±standard deviation) age of fresh and old PRBCs was 4.9±2.2 and 32.8±11.8 days, respectively. Six-hour mechanical damage of fresh PRBCs was demonstrated by increased erythrocyte fragmentation rates (p=0.015), hemolysis rates (p=0.003), and supernatant potassium levels (p=0.003) and decreased hematocrit levels (p=0.015). Old PRBC hemolysis rates (p=0.015), supernatant potassium levels (p=0.015), and supernatant hemoglobin (p=0.015) were increased and hematocrit levels were decreased (p=0.015) within 6 h. Two (13%) units of fresh PRBCs and none of the old PRBCs were eligible for transfusion after 6 h of mechanical stress. Conclusion: When an austere combat environment was simulated for 24 h, fresh and old PRBC hemolysis rates were above the quality criteria. Currently, the technology to overcome this mechanical damage does not seem to exist. In light of the above data, a new national project is being performed.