Chemokine (C-C motif) ligand-2 (CCL2) and oxidative stress markers in recurrent pregnancy loss and repeated implantation failure.

PURPOSE: The main purpose of this study is to evaluate the inflammatory response and oxidative stress together in the cases of recurrent pregnancy loss (RPL) and repeated implantation failure (RIF). METHODS: This is a cross-sectional study conducted to compare infertile patients who have RIF and patients with RPL histories in terms of CCL2, TAS, TOS, and OSI. To this end, two study groups were formed by primary-infertile women with RIF history and women with nulliparous RPL history who consulted a university hospital between 2014 and 2016, and a control group was formed by multiparous women who had no pregnancy loss. With 30 women in each group, 90 women in total were included in the study. CCL2, TAS, and TOS blood levels were measured and oxidative stress index was calculated in all participants. RESULTS: The patients with RPL and RIF had higher levels of CCL2 than those in the control group. The TOS, TAS, and OSI levels did not differ in RPL and RIF groups from the control group. No statistically significant relationship was found between CCL2 and the TOS, TAS, and OSI values. CONCLUSIONS: Oxidative stress markers in the pregestational period did not have a predictive value in the RPL and RIF. CCL2 might be useful in risk prediction.

Galectin-3: A biochemical marker to detect paroxysmal atrial fibrillation?

PURPOSE: Atrial fibrillation (AF) is the most common form of arrhythmia. AF leads to electrical remodelling and fibrosis of the atria; however, the mechanism(s) remain poorly understood. Galectin-3 is a potential mediator of cardiac fibrosis. The present study aimed to examine the relationship between serum galectin-3 levels and paroxysmal AF. METHODS: Forty-six patients with paroxysmal AF and preserved left ventricular systolic function, and 38 age- and gender-matched control subjects, were involved in the study. Serum galectin-3 levels were analyzed with an enzyme-linked immunosorbent assay (ELISA). RESULTS: Serum galectin-3 levels (median 1.38 ng/mL; 1.21 ng/mL-1.87 ng/mL; p< 0.001) were significantly elevated in patients with paroxysmal AF compared with the control. Left atrial diameter was significantly higher in patients with paroxysmal AF (41.2±3.0 mm vs. 39.6±3.3 mm). Left atrial diameter was found to be significantly correlated with serum galectin-3 levels in patients with paroxysmal AF (r= 0.378, p= 0.001). CONCLUSION: Serum galectin-3 levels are significantly elevated and significantly correlated with left atrial diameter in patients with paroxysmal AF.

Oxidant/antioxidant balance in the aqueous humor of patients with glaucoma.

AIM: To evaluate total antioxidant status (TAS), total oxidant status (TOS), and the oxidative stress index (OSI) of the aqueous humor (AH) in patients with glaucoma. METHODS: The prospective study was composed of a study group (n=31) and a control group (n=31). Fifteen patients in the study group were diagnosed with primary open angle glaucoma (POAG), and 16 patients were diagnosed with pseudoexfoliation glaucoma (PEG). The control group was composed of non-glaucomatous patients with cataracts. AH samples were collected and analyzed for TAS, TOS, and OSI levels. RESULTS: Mean AH TAS level was significantly higher in patients with glaucoma than that in the control group (P<0.01). Mean TOS and OSI levels tended to increase in patients with glaucoma. No significant differences in TAS, TOS, or OSI levels were observed between patients with POAG and PEG. CONCLUSION: High levels of TAS were observed in patients with glaucoma, which was likely a response to the increased oxidative stress observed in these patients.

Adipokine, adropin and endothelin-1 levels in intrauterine growth restricted neonates and their mothers.

Intrauterine growth retardation/restriction (IUGR) is associated with fetal malnutrition. It has consequences for later life including increased incidence of obesity, diabetes mellitus, cardiovascular disease (CVD), and metabolic syndrome. Adipokines (adiponectin and leptin), adropin, and endothelin-1 are associated with obesity and metabolic syndrome regulation. Intrauterine changes in these mediators could affect programming of later adult obesity and metabolic syndrome. Our objectives were to compare the levels of these mediators in both cord and maternal blood between IUGR pregnancies and control, healthy pregnancies, and to study the correlation of adipokines with adropin and endothelin-1 in maternal and cord blood in IUGR pregnancies as well as in healthy control pregnancies. Maternal and cord blood samples were taken from 16 women with IUGR pregnancies and 16 women with healthy pregnancies. Serum levels of leptin, adiponectin, adropin, and endothelin-1 were measured by ELISA. Maternal blood adropin levels were significantly lower in the IUGR group than in the control group; the other mediators did not differ significantly. There was a positive correlation between maternal blood adropin and endothelin levels. (r=0.731, P=0.001) in the control but not the IUGR group. Cord blood adropin and adiponectin levels were significantly lower in the IUGR group compared with the control group, while leptin or endothelin-1 did not differ significantly. There was a negative correlation between adropin and leptin (r=-0.704, P=0.001) in the IUGR but not the control group cord blood. There were also positive correlations between endothelin and adropin for both groups (r=0.594, P=0.006; r=0.560, P=0.010, respectively); to the best of our knowledge, this is the first report of such a correlation. Differences in fetal expression of adropin and adiponectin in IUGR could influence programming of obesity, metabolic syndrome, diabetes, and CVD in later life.

Galectin-3 as a new biomarker of diastolic dysfunction in hemodialysis patients.

BACKGROUND: Galectin-3 (gal-3) is an emerging prognostic biomarker in heart failure (HF). Clinical and experimental studies suggest that gal-3 is an important mediator of HF. Here we aimed to examine the relationship between gal-3 and diastolic dysfunction in patients undergoing maintenance hemodialysis (HD). METHODS: We examined the relationship between plasma gal-3 levels and left ventricular diastolic function. Plasma gal-3 was measured in 87 subjects with chronic HD and in 45 healthy controls using biochemical evaluations. Conventional echocardiography and pulsed tissue Doppler assessment were performed in all patients. Left ventricular diastolic dysfunction (LVDD) was defined as E' < 8 cm/s. The E/E' ratio was used as the main determinant of LVDD grade. RESULTS: The mean gal-3 concentrations were: 16.05 ng/ml (13.89-19.75) in healthy controls; 14.54 ng/ml (10.85-17.65) in HD patients with normal diastolic function; and 23.30 ng/ml (20.12-26.87) in HD patients with LVDD (p < 0.01). Plasma gal-3 levels correlated with E/E' (r = 0.933, p < 0.01), left atrial volume index (r = 0.713, p < 0.01), and E' (r = -0.685, p < 0.01). ROC analysis showed that the best gal-3 cut-off point for the diagnosis of LVDD was 20.12 ng/ml with a sensitivity of 67.6 % and specificity of 84.6 % (AUC = 0.803). CONCLUSION: We suggest that gal-3 may be a promising biomarker for the detection of LVDD in HD patients.

The impact of pretreatment with bolus dose of enteral glutamine on acute lung injury induced by oleic acid in rats.

PURPOSE: Both parenteral and enteral glutamine have shown beneficial effects in sepsis and ischemia/reperfusion-induced acute lung injury (ALI). Oleic acid (OA) has been used to induce ALI in experimental studies. In this study, we investigated the effects of pretreatment of a bolus dose of enteral glutamine on ALI induced by OA in rats. METHODS: Twenty-eight adult female Sprague-Dawley rats weighing 240-300 g were divided into four groups, 7 in each. Group I and group II received normal saline for 30 days, group III and group IV received glutamine at a dose of 1 g/kg for 10 days by gavage, and in group II and group IV 100 mg/kg OA was administered i.v. Histopathological examination of the lung was performed with light and electron microscopy. Levels of protein carbonyl, malondialdehyde, superoxide dismutase, catalase, and glutathione peroxidase levels were measured in tissue samples. Levels of tumor necrosis factor (TNF)-α, interleukin (IL)-6, IL-10, and total tissue oxidant status and total tissue antioxidant status were measured in serum samples. RESULTS: Light microscopy showed that the total lung injury score of group IV was significantly lower than group II. Change in thickness of the fused basal lamina was not significantly different in groups II and IV under electron microscopy. TNF-α, IL-6, and IL-10 serum levels were higher in group II when compared to group I and significantly attenuated in group IV. CONCLUSION: Pretreatment with a bolus dose of enteral glutamine minimized the extent of ALI induced by OA in rats.

Generation of Chimeric "ABS Nanohemostat" Complex and Comparing Its Histomorphological In Vivo Effects to the Traditional Ankaferd Hemostat in Controlled Experimental Partial Nephrectomy Model.

Purpose. Using the classical Ankaferd Blood Stopper (ABS) solution to create active hemostasis during partial nephrectomy (PN) may not be so effective due to insufficient contact surface between the ABS hemostatic liquid agent and the bleeding area. In order to broaden the contact surface, we generated a chimeric hemostatic agent, ABS nanohemostat, via combining a self-assembling peptide amphiphile molecule with the traditional Ankaferd hemostat. Materials and Methods. In order to generate ABS nanohemostat, a positively charged Peptide Amphiphile (PA) molecule was synthesized by using solid phase peptide synthesis. For animal experiments, 24 Wistar rats were divided into the following 4 groups: Group 1: control; Group 2: conventional PN with only 0.5 ml Ankaferd hemostat; Group 3: conventional PN with ABS + peptide gel; Group 4: conventional PN with only 0.5 ml peptide solution. Results. Mean warm ischemia times (WITs) were 232.8 ± 56.3, 65.6 ± 11.4, 75.5 ± 17.2, and 58.1 ± 17.6 seconds in Group 1 to Group 4, respectively. Fibrosis was not different among the groups, while inflammation was detected to be significantly different in G3 and G4. Conclusions. ABS nanohemostat has comparable hemostatic efficacy to the traditional Ankaferd hemostat in the partial nephrectomy experimental model. Elucidation of the cellular and tissue effects of this chimeric compound may establish a catalytic spark and open new avenues for novel experimental and clinical studies in the battlefield of hemostasis.

Elevated serum angiotensin converting enzyme levels as a reflection of bone marrow renin-angiotensin system activation in multiple myeloma.

INTRODUCTION: Angiotensin converting enzyme (ACE) is a circulating enzyme that participates in the body's renin-angiotensin system (RAS) and is localized on the endothelial cell surface in the lung and other vascular beds. It catalyses the conversion of decapeptide angiotensin I to octapeptide angiotensin II. In the present study, we aimed to analyse the possible relationship between the levels of ACE in the context of RAS in multiple myeloma (MM) pathogenesis. MATERIALS AND METHODS: The study was conducted on 25 MM patients (13 males, 12 females; median age 66 years, range 47-88) and 20 healthy controls. The clinical features of MM patients including demographics and laboratory findings were summarized. Serum ACE levels were measured by using commercially available kits. RESULTS: The serum ACE levels of MM patients and controls were 32.60±20.26 and 15.35±6.47 respectively. Serum ACE levels were significantly higher in MM patients compared with control groups (p<0.001). CONCLUSIONS: Being an important component of RAS, circulating ACE might be associated with clonal proliferation of malignant plasma cells in the bone marrow microenvironment. Identification of the pathobiological activity of the local RAS in MM would enlighten the biologic basis and clinical management of haematologic disorders.

Serum angiotensin-converting enzyme level as a marker of fibrosis in patients with chronic hepatitis B.

BACKGROUND: and aims: Hepatitis B virus (HBV) infection is a public health problem and affects nearly 350 million people worldwide. The present study was conducted in order to investigate the role of circulating angiotensin-converting enzyme (ACE) in the context of renin-angiotensin-aldosterone in newly diagnosed chronic hepatitis B infection. Moreover the association between liver fibrosis and serum ACE levels was also investigated. MATERIALS AND METHODS: The study was performed on 50 chronic hepatitis B (CHB) patients (24 males, 26 females; median age 39.4 years, range 18-63) and 20 healthy controls. The clinical features of CHB patients including demographics, laboratory and liver biopsy findings were summarized. Serum ACE levels were measured by using commercially available kits. RESULTS: Serum median ACE levels were 48.4 (14-83) U/L and 26.2 (12-48) U/L for the CHB patients and controls, respectively. Serum ACE levels were significantly higher in patients with CHB compared with the control group (p<0.001). Twenty-two patients (44%) had advanced liver fibrosis (Ishak score >2) and 28 patients (56%) had mild liver fibrosis (Ishak score ≤ 2). Mean serum levels of ACE were significantly higher among patients with advanced fibrosis as compared with those without advanced fibrosis (60.3±14.2 U/L vs. 39.0±10.5 U/L, p<0.001). Receiver operating characteristic (ROC) curve analysis suggested that the optimum ACE level cut-off point for advanced fibrosis was 52.5 U/L (sensitivity: 81.8%, specificity: 82.1%, PPV 78.3%, NPV 85.2%, accuracy 82%, AUC: 0.890). CONCLUSIONS: Our study showed that elevated circulating ACE levels are commonly observed in CHB patients. This finding was more prominent in patients with advanced fibrosis in liver. When evaluating a patient along with other parameters, the inclusion of ACE levels in the evaluation of CHB patients may grant additional prognostic information.

Serum adenosine deaminase activity as a predictor of disease severity in ulcerative colitis.

BACKGROUND AND AIM: Ulcerative colitis (UC) is a chronic inflammatory disease characterized by recurrent inflammation and ulcerations of colonic mucosa and an inappropriate and delayed healing. Adenosine deaminase (ADA) is a cytoplasmic enzyme involved in the catabolism of purine bases, capable of catalyzing the deamination of adenosine, forming inosine in the result process. Although ADA has been shown to increase in several inflammatory conditions, there are no literature data indicating an alteration in UC. METHODS: This study evaluated the activity of total ADA in serum of 43 patients with UC and 18 healthy controls. Patients' age, disease duration, drug intake, and other medical history were all noted for each subject. Complete blood count, erythrocyte sedimentation rate (ESR), and C-reactive protein (CRP) were determined for both patients and controls. Correlation analysis was also performed between ADA and other inflammation markers of UC. RESULTS: Serum mean ADA levels were 11.12 ± 2.03 and 7.99 ± 2.04 U/l for patients with UC in active state and in remission and 8.55 ± 2.26 U/l in the healthy control group. Mean serum ADA levels were significantly elevated in active UC patients compared with patients with UC in remission and control groups. Overall accuracy of ADA in determination of active UC was 83.7 with sensitivity 83.3%, specificity 84.2%. CONCLUSIONS: Serum ADA levels were found to be elevated in UC patients in active state suggesting a partial role of activated T-cell response in the disease pathophysiology. Further randomized controlled studies are warranted to demonstrate the role of ADA in UC patients, with a special interest in specifically targeted therapies against ADA for achieving disease remission.

Plasma thrombin-activatable fibrinolysis inhibitor as an indicator of inflammation and disease severity in acute pancreatitis.

AIM: In addition to suppressing fibrinolysis, thrombin activatable fibrinolysis inhibitor (TAFI) was suggested to be involved in inflammation. To date, no study has been published that reports the role of TAFI in acute pancreatitis (AP). Therefore, the objective of the present study was to investigate the role of plasma TAFI as an indicator of inflammation in AP, and its association with disease severity. METHODS: Plasma TAFI antigen levels quantitatively determined by using ELISA kits in 21 AP patients at onset and remission and 17 healthy controls. Associations of TAFI with inflammatory markers to determine AP and disease severity were assessed. To predict the severity of AP, modified Glasgow prognostic score (mGPS) and computerized tomography severity index (CTSI) were used for each subject. RESULTS: Plasma TAFI levels was higher in AP patients at onset of the disease compared with healthy controls. The disease severity according to mGPS was significantly correlated with TAFI levels. Overall, accuracy of TAFI in determining AP was 83.3% with a sensitivity, specificity, NPV and PPV of 80.9%, 85.7%, 81.8%, and 85% respectively (AUC: 0.915). CONCLUSIONS: The present study for the first time demonstrated that TAFI is elevated in AP. The appraisal of TAFI levels in patients with AP in conjunction with other markers of inflammation may provide additional information in estimating AP severity.

Increased ACE in extrahepatic cholangiocarcinoma as a clue for activated RAS in biliary neoplasms.

AIM: Cholangiocarcinoma (CCA) is a primary neoplastic tumor of the epithelial lining of the biliary tree which carries a poor prognosis despite combined therapeutic strategies. Although the exact etiology remains obscure, it has been suggested that locally produced Angiotensin II (Ang II) in intrahepatic CCA tissues plays a key role in the proliferation and activation of CCA. In the present study, we aimed to analyze the relationship between the levels of circulating angiotensin converting enzyme (ACE), an important molecule of the renin-angiotensin system (RAS), and biliary disorders. PATIENTS AND METHODS: The study group comprised 19 extrahepatic cholangiocarcinoma (EHCC) (16 patients with hilar, three patients with distal CCA), and 15 choledocolithiasis (CL) patients, with 15 controls. Median age of EHCC, CL and healthy controls were 67 (48-82), 65 (29-87) and 56 (23-74) respectively. ACE was measured by monitoring the alteration in absorbance at 340 nm of the hydrolysis of furylacrylolylphenylalanylglycylglycine (FAPGG) to FAP and GG on an analyzer. The ACE activity in the sample was determined by comparing the sample reaction rate to that obtained with the ACE calibrator. RESULTS: Serum mean ACE levels were 56.6±27.4 U/L, 32.9±14.6 U/L and 28.6±10.6 U/L for patients with EHCC, CL and healthy controls, respectively. Serum ACE levels were significantly higher in patients with EHCC compared to CL and control groups. No significant differences with respect to ACE levels were observed between CL and control groups. CONCLUSION: Circulating ACE in the context of RAS might be associated with EHCC development by creating a local environment enriched with cytokines and other growth factors that may promote cholangiocyte turnover.

Trace and toxic element patterns in nonsmoker patients with noninsulin-dependent diabetes mellitus, impaired glucose tolerance, and fasting glucose.

PROJECT: Noninsulin dependent diabetes mellitus is supposed to be associated with fluctuations in the plasma levels of several trace elements. There is accumulating evidence that the metabolism of several trace elements is altered in patients with noninsulin dependent diabetes mellitus and that these nutrients might have specific roles in the pathogenesis and progression of this disorder. PROCEDURE: The aim of the present study is to compare the levels of essential trace and toxic elements including lead (Pb), arsenic (As), cadmium (Cd), chromium (Cr), aluminium (Al), nickel (Ni), cobalt (Co), iron (Fe), copper (Cu), selenium (Se), zinc (Zn), vanadium (V), manganese (Mn), barium (Ba), silver (Ag), and mercury (Hg) in patients with noninsulin dependent diabetes mellitus (n = 31), impaired glucose tolerance (n = 20), impaired fasting glucose (n = 14), and healthy controls (n = 22). Plasma concentrations of the elements were measured by using inductively coupled plasma mass spectrometry. RESULTS: The results indicated that values of lead, nickel, aluminium, copper, and chromium were significantly higher, but not above toxic levels, in the plasma of nonsmoker patients with noninsulin dependent diabetes mellitus (P < 0.05). The values for these elements were found to be significantly higher (P < 0.05) in patients with impaired fasting glucose than in controls. Moreover, a statistically significant correlation was found between plasma levels of glycated hemoglobin and of some trace elements like lead, nickel, aluminium, copper, chromium, cadmium, and mercury. CONCLUSIONS: Thus, it was concluded that chronic complications of glucose metabolism disorders might be associated with alterations in the levels of some trace elements. Nevertheless, some more timely and extensive studies are required to clarify the exact mechanisms of each of these changes.