Sema Uysal

Uric Acid and Pentraxin-3 Levels Are Independently Associated with Coronary Artery Disease Risk in Patients with Stage 2 and 3 Kidney Disease

Background and Objectives: Cardiovascular disease is prevalent in chronic kidney disease (CKD). Uric acid is increased in subjects with CKD and has been linked with cardiovascular mortality in this population. However, no study has evaluated the relationship of uric acid with angiographically proven coronary artery disease (CAD) in this population. We therefore investigated the link between serum uric acid (SUA) levels and (i) extent of CAD assessed by the Gensini score and (ii) inflammatory parameters, including C-reactive protein (CRP) and pentraxin-3, in patients with mild-to-moderate CKD. Material and Methods: In an unselected population of 130 patients with estimated glomerular filtration rate (eGFR) between 90 and 30 ml/min/1.73 m2, we measured SUA, serum pentraxin-3, CRP, urinary protein-to-creatinine ratio, lipid parameters and the severity of CAD as assessed by coronary angiography and quantified by the Gensini lesion severity score. Results: The mean serum values for SUA, pentraxin-3 and CRP in the entire study population were 5.5 ± 1.5 mg/dl, 6.4 ± 3.4 ng/ml and 3.5 ± 2.6 mg/dl, respectively. The Gensini scores significantly correlated in univariate analysis with gender (R = –0.379, p = 0.02), uric acid (R = 0.42, p = 0.001), pentraxin-3 (R = 0.54, p = 0.001), CRP (R = 0.29, p = 0.006) levels, eGFR (R = –0.33, p = 0.02), proteinuria (R = 0.21, p = 0.01), and presence of hypertension (R = 0.37, p = 0.001), but not with smoking status, diabetes mellitus, and lipid parameters. After adjustments for traditional cardiovascular risk factors, only uric acid (R = 0.21, p = 0.02) and pentraxin-3 (R = 0.28, p = 0.01) remained significant predictors of the Gensini score. Conclusions: SUA and pentraxin-3 levels are independent determinants of severity of CAD in patients with mild-to-moderate CKD. We recommend a clinical trial to determine whether lowering uric acid could prevent progression of CAD in patients with CKD.

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

OBJECTIVES The relation between nonalcoholic steatohepatitis and iron metabolism is still controversial. Free fatty acids, iron, and other sources of oxidative stress probably result in cell damage, and necroinflammation mediated by various cytokines. DESIGN AND METHODS Sixty patients were diagnosed with NASH were included in the study, and the patient group was divided into three subgroups. Iron metabolism markers, inflammatory cytokines, including TNF-α, IL-6 and IL-8, MDA and nitric oxide levels were measured. RESULTS Serum ferritin, inflammatory cytokines, and oxidative stress markers were significantly higher in the patient group. Among three patient groups, divided according to the results of ultrasonic examination, there were significant changes with regard to these parameters. CONCLUSION The study results suggest that liver iron and fat accumulation, oxidant stres, and inflammatory cytokines are closely related. Therefore, levels of serum ferritin, MDA, IL-6, TNF-α and IL-8 could represent the indices of activity and progression of NASH.

Hepcidin, iron status, and inflammation variables among healthy pregnant women in the Turkish population

Abstract Purpose: To investigate hepcidin levels in each trimester and their association with other haematological variables and inflammation markers during normal pregnancy among low-risk pregnant women in rural Turkey. Method: The series comprised 103 healthy Turkish primigravida women with a normal pregnancy. Blood samples were obtained at 11–14, 24–28 and 30–34 weeks of gestation. Haemoglobin, hematocrit, red cell indices, white blood cell count, platelet count, iron status indicators (plasma iron, transferrin, ferritin levels and iron binding capacity), serum hepcidin, interleukin-6 and C-reactive protein levels were analysed. The proportions were compared using Pearson’s χ2 test or Friedman’s test. Results: The mean serum hepcidin concentrations at 11–14, 24–28 and 30–34 weeks of gestation were as follows: 7.8 ± 3.4 ng/mL, 8.6 ± 3.1 ng/mL and 7.3 ± 3.0 ng/mL, respectively. The mean serum ferritin concentrations with median values at each trimester were 14.2 (11.5), 9.5 (8.8) and 11.2 (9.3), respectively. The mean serum CRP values at each trimester were 5.1 (4.0), 5.5 (4.6) and 6.0 (5.5), respectively. The serum hepcidin levels were not related to iron status or the haemoglobin, IL-6 or C-reactive protein levels. Conclusions: There was no association between serum hepcidin and serum ferritin, IL-6 or CRP concentrations in each trimester among low-risk pregnant women.

Evaluating vaspin and adiponectin in postmenopausal women with endometrial cancer.

Insulin resistance is a well-documented risk factor for the development of endometrial cancer. Adiponectin and vaspin are insulin-sensitizing proteins that are secreted from adipose tissue. A clear association between serum levels of adipokines and endometrial cancer has yet to be established. The study group consisted of postmenopausal women with confirmed endometrial cancer, whereas patients with benign endometrial conditions constituted the control group. The two groups were compared in terms of insulin resistance and serum levels of adiponectin and vaspin. A total of 60 patients with confirmed endometrial cancer and 70 controls with benign endometrial conditions (polyps and atrophy) were enrolled. Median homeostasis model assessment of insulin resistance value was significantly higher in the study group compared with the control group (2.93 vs 1.27, P<0.0001), whereas mean quantitative insulin sensitivity check index value was significantly lower (0.33 ± 0.02 vs 0.37 ± 0.37, P<0.0001). Median values for both adiponectin and vaspin were significantly lower in patients with endometrial cancer compared with the control group (4.09 vs 17.13 μg/ml, P<0.0001 and 0.21 vs 0.39 ng/ml, P<0.0001 respectively). Low levels of both adiponectin and vaspin were found to be significantly associated with an increased risk for endometrial cancer. Following adjustment for confounding factors, the respective odds ratios for endometrial cancer in patients in the first tertile compared with those in the third tertile were 10.80 (2.76-42.24; P=0.001) and 13.23 (2.94-59.64; P=0.001). Our results show that lower levels of circulating adiponectin and vaspin levels are associated with an increased risk of developing endometrial cancer.

The diagnostic value of non-invasive tests for the evaluation of liver fibrosis in chronic hepatitis B patients

Abstract Background. Liver biopsy, which is considered the gold standard for the evaluation of hepatic fibrosis in patients with chronic hepatitis B (CHB), has certain limitations. The aim of this study was to investigate the diagnostic performance of non-invasive markers of hepatic fibrosis as potential alternatives to liver biopsy. Methods. The medical records of 221 patients with a diagnosis of CHB who underwent a liver biopsy were reviewed. Indirect indicators of fibrosis were calculated for each patient based on previously described formulas [Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) ratio (AAR), age-platelet index (API), cirrhosis discriminant score (CDS), AST-platelet ratio index (APRI), Forns index, FIB-4, Pohl score, AAR-platelet score (AARP), fibro-quotient (FibroQ), AST/platelet/Gammaglutamyl transpeptidase (GGT)/Alphafetoprotein (AFP) (APGA) index, Platelet/Age/Phosphatase (ALP)/AFP/AST (PAPAS) index, Loks model, Goteborg University Cirrhosis Index (GUCI)]. Diagnostic adequacy of these indices was evaluated by receiver operating characteristic curve analysis. Results. Area under the receiver operating characteristic curves for the FIB-4, Forns, GUCI, APRI, PAPAS, APGA and FibroQ indices were 0.701, 0.680, 0.670, 0.670, 0.639, 0.638 and 0.588, respectively. The AAR, API, CDS and AARP indices, Pohl score and Loks model were all deemed diagnostically inadequate. FIB-4 had the best diagnostic adequacy whereas AAR had the worst. Conclusions. Our results suggest that out of the 13 indices evaluated, only FIB-4 index may be useful in estimating the extent of fibrosis in patients with CHB. There is a need for more comprehensive prospective studies to help determine the diagnostic value of non-invasive tests for liver fibrosis.

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

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

Thrombopoietin and Mean Platelet Volume in Patients With Ischemic Stroke

Objective: The aim of this study was to evaluate mean platelet volume (MPV), thrombopoietin (TPO), and platelet levels in patients with ischemic stroke and compare this with healthy controls. Methods: We prospectively studied 50 patients with ischemic stroke and compared them with 37 control participants who have evaluated in internal medicine polyclinic and had no history of cerebrovascular events. All patients were within 24 hours after stroke; MPV and TPO were measured on admission. Results: Both TPO and MPV values were significantly higher in patients with stroke (P = .00; P = .001). Conclusion: Increased TPO levels may increase both platelet count and platelet size, resulting in more hemostatic tendency, which may contribute to the progression of ischemic stroke.

Efectos protectores del aceite de Nigella sativa en la lesión pulmonar inducida por hiperoxia

BACKGROUND Oxygen-induced lung injury is believed to lead to the development of bronchopulmonary dysplasia in premature infants. We have evaluated the beneficial effects of Nigella sativa oil (NSO) on rats with hyperoxia-induced lung injury. METHODS Thirty newborn Sprague-Dawley rats were randomly divided into 3 groups as hyperoxia (95% O(2)), hyperoxia+NSO and control (21% O(2)). Pups in the hyperoxia+NSO group were administered intraperitoneal NSO at a dose of 4ml/kg daily during the study period. Histopathologic, immunochemical, and biochemical evaluations (superoxide dismutase [SOD], glutathione peroxidase [GSH-Px], malonaldehyde [MDA] and myeloperoxidase [MPO]) were performed. RESULTS In the histopathologic and immunochemical evaluation, severity of lung damage was significantly lower in the hyperoxia+NOS group (P<.05). Tissue GSH-Px and SOD levels were significantly preserved, and MDA, MPO levels were significantly lower in the hyperoxia+NSO group (P<.05). CONCLUSION NSO significantly reduced the severity of lung damage due to hyperoxia.

N-acetylcysteine may prevent severe intestinal damage in necrotizing enterocolitis

OBJECTIVE The aim of this study was to evaluate the preventive effect of N-acetylcysteine (NAC) on the development of necrotizing enterocolitis (NEC) in an experimental rat model. MATERIAL AND METHODS Thirty newborn Sprague-Dawley rats were randomly divided into 3 groups: NEC, NEC + NAC, and control. Necrotizing enterocolitis was induced by enteral formula feeding, exposure to hypoxia-hyperoxia, and cold stress. Pups in the NEC + NAC group were administered NAC at a dose of 150 mg/kg daily by intraperitoneal route from the first day until the last day of the study. All pups were killed on the fifth day. Proximal colon and ileum were excised for histopathologic, immunohistochemical (terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate-biotin nick end-labeling and caspase-3, caspase-8, caspase-9), and biochemical evaluation, including xanthine oxidase, total antioxidant status, total oxidant status, malondialdehyde, and myeloperoxidase activities. RESULTS The pups in the NEC + NAC group had better clinical sickness scores compared with those in the NEC group (P < .05). In histopathologic and apoptosis evaluations (terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate-biotin nick end-labeling and immunohistochemical evaluation for caspase-3 and caspase-9), the severity of bowel damage was significantly less in the NEC + NAC group compared with the NEC group (P < .01). Tissue malondialdehyde, myeloperoxidase, xanthine oxidase levels, and total oxidant status were significantly decreased in the NEC + NAC group, whereas total antioxidant status (TAS) was significantly increased in the NEC + NAC group (P < .01). CONCLUSION N-acetylcysteine therapy significantly reduced the severity of intestinal damage in NEC.

Augmentation of ADAMTS9 gene expression by IL-1β is reversed by NFκB and MAPK inhibitors, but not PI3 kinase inhibitors.

The pathways involved in the regulation of a disintegrin and metalloproteinase with thrombospondin motifs 9 (ADAMTS9) expression have not yet been elucidated. Therefore, the aim of this study was to investigate the involvement of nuclear factor‐κB (NF‐κB), mitogen activated protein kinases (MAPK) and Phosphatidylinositol 3‐kinase (PI3 kinase) in ADAMTS9 gene regulation, with special focus on the involvement of NF‐κB in IL‐1β‐induced ADAMTS9 expression. The OUMS‐27 chondrosarcoma cells were exposed to IL‐1β. They were pretreated with 20 μM PD98059 (specific inhibitor of p44/42 kinase), 10 μM SB203580 (specific inhibitor of p38 kinase), 20 μM SB600125 (MAPK inhibitor), and 1 μM Wortmannin and 10 μM LY294002 (specific inhibitors of PI3 kinase) for 30 min and subsequently incubated with IL‐1β. For the effects of NF‐κB and IκB inhibitors, cells were pretreated with curcumin or BAY117085 for 30 min and subsequently incubated with IL‐1β. BAY117085 and different concentrations of curcumin were applied to the cells just after the first experiment to determine their concentration effect on ADAMTS9 gene expression. After total RNA was extracted, they were reversely transcribed with random primers and then real‐time polymerase chain reaction (PCR) was performed on cDNA samples.