Artificial neuronal network analysis in investigating the relationship between oxidative stress and endoplasmic reticulum stress to address blocked vessels in cardiovascular disease.

Background: Cardiovascular disease is the leading cause of death in the world and is associated with significant morbidity. Atherosclerosis is the main cause of cardiovascular disease (CVD), including myocardial infarction (MI), heart failure, and stroke. The mechanism of atherosclerosis has not been well investigated in different aspects, such as the relationship between oxidative stress and endothelial function. This project aims to investigate whether an oxidative enzyme vascular peroxidase 1 (VPO1) and activating transcription factor 4 (ATF4) can be used as biomarkers in highlighting the pathogenesis of the disease and in evaluating the prognosis of the relationship with endoplasmic reticulum and oxidative stress. This paper used artificial neural network analysis to predict cardiovascular disease risk based on new generation biochemical markers that combine vascular inflammation, oxidative and endoplasmic reticulum stress. Methods: For this purpose, 80 patients were evaluated according to the coronary angiography results. hs-CRP, lipid parameters and demographic characteristics, VPO1, ATF4 and Glutathione peroxidase 1(GPx1) levels were measured. Results: We found an increase in VPO1 and hs-CRP levels in single-vessel disease as compared to controls. On the contrary, ATF4 and GPx1 levels were decreased in the same group, which was not significant. Our results showed a significant positive correlation between ATF4 and lipid parameters. A statistically significant positive correlation was also observed for VPO1 and ATF4 (r=0.367, P<0.05), and a negative correlation was found for ATF4 and GPx1 (r=-0.467, P<0.01). A significant negative relationship was noted for GPx1 and hs-CRP in two/three-vessel disease (r=-0.366, P<0.05). Artificial neural network analysis stated that body mass index (BMI) and smoking history information give us an important clue as compared to age, gender and alcohol consumption parameters when predicting the number of blocked vessels. Conclusions: VPO1 and ATF4 might be potential biomarkers associated with coronary artery disease, especially in the follow-up and monitoring of treatment protocols, in addition to traditional risk factors.

Cerebral Venous Sinus Thrombosis in Women: Subgroup Analysis of the VENOST Study.

BACKGROUND: Early diagnosis of cerebral venous sinus thrombosis (CVST) associated with reproductive health-related risk factors (RHRF) including pregnancy, puerperium, and oral contraceptive (OC) use can prevent severe neurological sequelae; thus, the symptoms must be documented in detail for each group. METHODS: Out of 1144 patients with CVST, a total of 777 women were enrolled from a multicenter for the study of cerebral venous sinus thrombosis (VENOST). Demographic, biochemical, clinical, and radiological aspects were compared for 324 cases with RHRF and 453 cases without RHRF. RESULTS: The mean age of the RHRF (-) group (43.2 ± 13 years) was significantly higher than of the RHRF (+) group (34 ± 9 years). A previous history of deep venous thrombosis (3%), isolated cavernous sinus involvement (1%), cranial neuropathy (13%), comorbid malignancy (7%), and its disability scores after 12 months (9%) were significantly higher in the RHRF (-) group. The RHRF (+) group consisted of 44% cases of puerperium, 33% cases of OC users and 23% of pregnant women. The mean age was found to be higher in OC users (38 ± 9 years). A previous history of deep venous thrombosis was slightly higher in the pregnancy subgroup (4%). Epileptic seizures were more common in the puerperium group (44%). CONCLUSION: The results of our study indicate that the risk of CSVT increases parallel to age, OC use, and puerperium period. In addition, when considering the frequency of findings and symptoms, epileptic seizures in the puerperium subgroup of the RHRF (+) group and malignancies in the RHRF (-) group may accompany the CSVT. In daily practice, predicting these risks for the CSVT and early recognition of the symptoms will provide significant benefits to patients.

The relationship between the findings of vestibular evoked myogenic potentials and severity of obstructive sleep apnea syndrome.

PURPOSE: Our study aimed to evaluate the effects of chronic hypoxic state in Obstructive Sleep Apnea Syndrome (OSAS) on brainstem pathways using Vestibular Evoked Myogenic Potential (VEMP) test and to investigate the presence of new markers likely to be correlated with the severity of the disease. METHODS: The study was planned as prospective and double blind. A total of 60 patients (120 ears) diagnosed with mild, moderate and severe OSAS were included in the study and the patients are grouped as 20 patients in each group. Twenty volunteer healthy individuals (40 ears) shown to be without OSAS were included in the study. VEMP measurements were made in 60 study group patients (120 ears) and in 20 healthy controls (40 ears). The groups were compared in terms of variables such as the acquisition rate of oVEMP and cVEMP waves, interval between the waves, latency and amplitude of the waves. p < 0.05 values were considered as significant. RESULTS: The results of cVEMP test showed that the rate of wave acquisition in the moderate and severe OSAS groups was significantly lower than the control group and mild OSAS groups (p = 0.008). There was no difference between the control group and the mild OSAS group in terms of the rate of obtaining the wave (p > 0.05). In the moderate and severe OSAS groups, P1N1 amplitude and N1P2 amplitude values were found to be significantly lower than the mild OSAS group (p = 0.007 and p = 0.017, respectively). In the oVEMP test, there was no significant difference between the mild OSAS group and the control group in terms of the wave yield (p > 0.05); however, it was found that the rate of wave acquisition in the moderate and severe OSAS groups was significantly lower than the mild OSAS group (p = 0.041). There was inverse correlation between the N1P2 interval and P1N1 amplitude value and AHI in simple regression analysis and multiple regression analysis (p = 0.012 and p = 0.021; p = 0.009 and p = 0.040, respectively). CONCLUSION: The negative effects of chronic intermittent hypoxia related with OSAS on the brainstem and vestibular system can be demonstrated by VEMP tests. Especially, the inability to obtain the wave is the most important finding showing this situation. Also, we think that N1P2 interval and P1N1 amplitude markers can be used to detect the subclinical negative effect of chronic hypoxia on vestibular nuclei in the brainstem.

Protective effects of pentoxifylline in small intestine after ischemia-reperfusion.

Objective This study was performed to determine the healing effects of pentoxifylline on molecular responses and protection against severe ischemic damage in the small intestine. Methods Thirty-six Wistar albino rats were divided into six groups. The superior mesenteric artery was clamped for 120 minutes, and reperfusion was performed for 60 minutes. Saline (0.4 mL), pentoxifylline (1 mg/kg), and pentoxifylline (10 mg/kg) were intraperitoneally administered to the rats in the C1, P1, and P3 groups, respectively, 60 minutes before ischemia and to the rats in the C2, P2, and P4 groups, respectively, during reperfusion onset. Malondialdehyde, myeloperoxidase, tumor necrosis factor alpha, interleukin-1 beta, and interleukin-6 in serum and tissue were measured by enzyme-linked immunosorbent assay. Intestinal ischemic injury was histopathologically evaluated by the Chiu score and immunohistochemical staining. Results All serum and tissue molecular responses were significantly blunted in the pentoxifylline-treated groups compared with the controls. Significant improvement in ischemic damage was demonstrated in the pentoxifylline-treated groups by histological grading and immunohistochemical scoring. Conclusions The protective effects of pentoxifylline were confirmed by molecular responses and histopathological examination.

A database for screening and registering late onset Pompe disease in Turkey.

The aim of this study was to search for the frequency of late onset Pompe disease (LOPD) among patients who had a myopathy with unknown diagnosis registered in the pre-diagnostic part of a novel registry for LOPD within a collaborative study of neurologists working throughout Turkey. Included in the study were 350 patients older than 18 years who have a myopathic syndrome without a proven diagnosis by serum creatine kinase (CK) levels, electrodiagnostic studies, and/or muscle pathology, and/or genetic tests for myopathies other than LOPD. Acid alpha glucosidase (GAA) in dried blood spot was measured in each patient at two different university laboratories. LOPD was confirmed by mutation analysis in patients with decreased GAA levels from either both or one of the laboratories. Pre-diagnostic data, recorded by 45 investigators from 32 centers on 350 patients revealed low GAA levels in a total of 21 patients; from both laboratories in 6 and from either one of the laboratories in 15. Among them, genetic testing proved LOPD in 3 of 6 patients and 1 of 15 patients with decreased GAA levels from both or one of the laboratories respectively. Registry was transferred to Turkish Neurological Association after completion of the study for possible future use and development. Our collaborative study enabled collection of a considerable amount of data on the registry in a short time. GAA levels by dried blood spot even from two different laboratories in the same patient may not prove LOPD. LOPD seemed to be rarer in Turkey than in Europe.

Vagus Nerve Stimulation.

BACKGROUND: The vagus nerve stimulation (VNS) is an approach mainly used in cases of intractable epilepsy despite all the efforts. Also, its benefits have been shown in severe cases of depression resistant to typical treatment. AIM: The aim of this study was to present current knowledge of vagus nerve stimulation. MATERIAL AND METHODS: A new value has emerged just at this stage: VNS aiming the ideal treatment with new hopes. It is based on the placement of a programmable generator on the chest wall. Electric signals from the generator are transmitted to the left vagus nerve through the connection cable. Control on the cerebral bioelectrical activity can be achieved by way of these signal sent from there in an effort for controlling the epileptic discharges. RESULTS: The rate of satisfactory and permanent treatment in epilepsy with monotherapy is around 50%. This rate will increase by one-quarters (25%) with polytherapy. However, there is a patient group roughly constituting one-thirds of this population, and this group remains unresponsive or refractory to all the therapies and combined regimes. The more the number of drugs used, the more chaos and side effects are observed. The anti-epileptic drugs (AEDs) used will have side effects on both the brain and the systemic organs. Cerebral resection surgery can be required in some patients. The most commonly encountered epilepsy type is the partial one, and the possibility of benefiting from invasive procedures is limited in most patients of this type. Selective amygdala-hippocampus surgery is a rising value in complex partial seizures. Therefore, as epilepsy surgery can be performed in very limited numbers and rather developed centres, success can also be achieved in limited numbers of patients. The common ground for all the surgical procedures is the target of preservation of memory, learning, speaking, temper and executive functions as well as obtaining a good control on seizures. However, the action mechanism of VNS is still not exactly known. On the other hand, it appears to be a reliable method that is tolerated well in partial resistant seizures. It has been observed that adverse effects are generally of mild-medium severity, and most of the problems can be eliminated easily through the re-adjustment of the stimulator. CONCLUSION: VNS, which is a treatment modality that will take place it deserves in epilepsy treatment with "the correct patient" and "correct reason", must be known better and its applications must be developed.

Relation of Biochemical Parameters with Flow-mediated Dilatation in Patients with Metabolic Syndrome.

BACKGROUND: Metabolic syndrome (MetS) is one of the high cardiovascular (CV) situations. Endothelial dysfunction, which is a common finding in patients with MetS, is related with increased CV risk. In patients with MetS, the effect of the major CV risk factors, not included in the MetS definition, on endothelial dysfunction is not well known. The aim of this study was to determine the effect of major CV risk factors such as gender, smoking, family history, and biochemical parameters on endothelial dysfunction in patients with MetS. METHODS: The study was performed between December 2010 and August 2014. A total of 55 patients (15 females and 40 males) with MetS and 81 healthy controls (37 females and 44 males) with a body mass index <25 kg/m2 were enrolled in the study. Endothelial dysfunction was measured by flow-mediated dilatation (FMD), oxidative stress parameters; high-sensitivity C-reactive protein (hs-CRP), oxidized low-density lipoprotein (ox-LDL), endothelial nitric oxide synthase (e-NOS), nitric oxide, and cell adhesion markers; von Willebrand factor, and e-selectin. Platelet aggregation (endothelial adenosine diphosphate), total platelet count, and mean platelet volume were additionally analyzed and demographic parameters were explored. Student's t- test, Mann-Whitney U-test, and Chi-square test were used to analyze the results. RESULTS: The fasting blood glucose (z= 3.52, P= 0.001), hs-CRP (z = 3.23, P= 0.004), ox-LDL (z = 2.62, P= 0.013), and e-NOS (z = 2.22, P= 0.026) levels and cardiac risk score (z = 5.23, P< 0.001) were significantly higher in patients with MetS compared with the control group. Smoking was correlated with decreased FMD (χ2 = 9.26, P= 0.002) in MetS patients but not in the control group. CONCLUSIONS: Increased ox-LDL, hs-CRP, and e-NOS are likely to be a result of oxidative stress, a condition in which an imbalance occurs between the production and inactivation of reactive nitrogen and oxygen species. In addition, in patients with MetS, smoking is independently related to endothelial dysfunction.

Anti-inflammatory and ultrastructural effects of Turkish propolis in a rat model of endotoxin-induced uveitis.

INTRODUCTION: Experimental animal models of acute uveitis, an inflammatory eye disease, can be established via endotoxin-induced inflammation. Propolis, a natural substance collected by honeybees from buds and tree exudates, has antioxidant, antibacterial, antiviral, and anti-inflammatory effects. We investigated the effects of propolis, obtained from the Sakarya province of Turkey, on endotoxin-induced uveitis using immunohistochemical, ultrastructural, and biochemical approaches. MATERIAL AND METHODS: Male Wistar albino rats (n = 6/group) received intraperitoneal (ip) lipopolysaccharide (LPS) endotoxin (150 µg/kg) followed by aqueous extract of propolis (50 mg/kg ip) or vehicle; two additional groups received either saline (control) or propolis only. After 24 h, aqueous humor (AH) was collected from both eyes of each animal for analysis of tumor necrosis factor-α (TNF-α) and hypoxia-inducible factor-1α (HIF-1α). Right eyeballs were paraffin-embedded for immunohistochemical staining of nuclear factor κB (NF-κB)/p65 and left eyeballs were araldite-embedded for ultrastructural analysis. RESULTS: Treatment of LPS-induced uveitis with propolis significantly reduced ciliary body NF-κB/p65 immunoreactivity and AH levels of HIF-1α and TNF-α. Ultrastructural analysis showed fewer vacuoles and reduced mitochondrial degeneration in the retinal pigment epithelium, as compared to the uveitis group. The intercellular spaces of the inner nuclear layer and outer limiting membrane were comparable with those of the control group; no polymorphonuclear cells or stasis was observed in intravascular or extravascular spaces. CONCLUSIONS: This is the first report demonstrating an anti-inflammatory effect of Turkish propolis in a rat model of LPS-induced acute uveitis, suggesting a therapeutic potential of propolis for the treatment of inflammatory ophthalmic diseases.

In Vitro Fertilization, Levels of Pro-Inflammatory Factors and Lipid Peroxidation.

BACKGROUND: Infertility is a problem concerning 10-15% of the individuals in the fertile period. This study investigated effects of proinflammatory factors as well as lipid hydroperoxides (LPO) levels upon in vitro fertilization (IVF) success. MATERIALS AND METHODS: In this prospective, non-randomized, controlled clinical study, sera obtained from 26 fertile (group-1), 26 infertile women before (group-2) and after (group-3) IVF treatment were analyzed. Leptin, leptin receptor, resistin, tumor necrosis factor-alpha (TNF-α), and C-reactive protein (CRP) were analyzed using enzyme-linked immunosorbent assay (ELISA). LPO was determined spectrophotometrically. Mann- Whitney U test, paired samples t test, Wilcoxon signed-rank test as well as Pearson correlation analysis by SPSS were performed for statistical analysis. RESULTS: TNF-α, resistin and LPO levels increased (P=0.020, P=0.003, P=0.001, respectively) in group-3 compared to group-2. A significant increase in LPO was noted both in group-2 and -3 compared to controls (P=0.000). LPO were higher in non-pregnants than pregnants in group-2. For pregnants, significant correlations were observed between leptin and resistin in group-2 and TNF-α and leptin in group-3. None of these correlations were found for the women, who could not conceive. CONCLUSION: LPO, leptin-resistin correlation, associations with TNF-α may be helpful during the interpretation of IVF success rates.

Adrenomedullin--A New Marker in Febrile Neutropenia: Comparison With CRP and Procalcitonin.

In this study, we aimed to determine serum adrenomedullin levels and compare them with levels of C-reactive protein (CRP) and procalcitonin (PCT). Cancer patients aged 0-18 years who experienced febrile neutropenia attacks were included in the study. Adrenomedullin, CRP, and PCT were analyzed at admission, day 3, and days 7-10 later. Fifty episodes of febrile neutropenia that developed in 37 patients were analyzed in this study. The mean age of the patients was 7.5 ± 4.7 (1-18) years. The patients had leukemia (73%), solid tumors (19%), and lymphoma (8%). The percentages of the patients in the clinically documented infection (CDI), fever of unknown origin (FUO), sepsis, and microbiological documented infection (MDI) categories were 34%, 34%, 20%, and 12%, respectively. During the study period, four patients were lost. In the MDI group, adrenomedullin levels on day 3 were significantly higher than those in the CDI and FUO groups. PCT levels were significantly higher in the sepsis group than those in the CDI group at admission, day 3, and days 7-10. In the sepsis group, PCT levels on days 7-10 days were significantly higher than those in the sepsis group. PCT values from the deceased patients on days 7-10 were significantly higher than those from patients who survived. CRP levels did not differ significantly among the febrile neutropenia groups. First, in our study, adrenomedullin was used as a biomarker in the febrile neutropenia episodes of children with cancer. Among adrenomedullin, CRP, and PCT, procalcitonin demonstrates the highest correlation with the severity of infection.

Serum endocan concentration in women with pre-eclampsia.

PURPOSE: To investigate serum endocan levels in pregnant subjects with and without pre-eclampsia. METHODS: This cross-sectional study was conducted on 49 pregnant women with pre-eclampsia and 32 healthy pregnant women matched for gestational age. Maternal levels of serum endocan were measured with the use of an enzyme-linked immunosorbent assay kit. RESULTS: Mean endocan levels were not significantly different among groups (10.7 ± 4.5 vs. 10.3 ± 3.2 ng/mL, p 0.763). Mean uterine artery PI and RI were higher in the pre-eclampsia group (p < 0.001, p < 0.001). Mean endocan levels were negatively correlated with BMI at the time of blood sampling (r = -0.247, p = 0.044). There was no correlations between mean endocan levels and all the others parameters. CONCLUSION: These findings suggest that the role of endocan in the pathogenesis of pre-eclampsia was not related to pre-eclampsia; hence, further studies are needed to investigate the role of endocan in the pathogenesis of pre-eclampsia.

Effect Transformation of the Micro Electrode Recording (MER) Data to Fast Fourier Transform (FFT) for the Main Target Nucleus Determination for STN-DBS.

INTRODUCTION: Advanced PD stimulation of the STN reduces tremor, rigidity, and bradykinesia. Due to hemorrhagic complications the use of micro electrode recordings during DBS operation was still questioning for some of surgeons. But use micro electrodes were still the best choice for the positioning during surgery of DBS. AIM: The aim of the current study was to investigate the effect transformation of the micro electrode recording data to fast fourier transform for the main target nucleus determination. This process needs a multidisciplinary approach from neurosurgery, neurology and specialists on electrophysiology such as biophysics. CASE REPORT: We present the case of a 63 year-old male with medically intractable PD is focused on behalf of the surgical treatment. Patient had a 4-year history of progressively severe hand tremor on right side. The patient was successfully treated unilaterally with the STN DBS.

Nontraditional risk factors in carotid artery disease.

Carotid atherosclerosis (AS) is one of the main risk factors for ischemic stroke. Our aim is to evaluate the nontraditional biochemical markers in asymptomatic and symptomatic patients with carotid artery plaque. This study was conducted on 55 patients: 43 with symptomatic and 12 with asymptomatic carotid artery disease. Lipoprotein (a) (Lp(a)), homocysteine, adiponectin, nitric oxide (NO), and tumor necrosis factor alpha (TNF-alpha) levels were measured in the plasma. The mean of total cholesterol, triglyceride, and homocysteine levels was significantly elevated in the symptomatic group as compared with the asymptomatic group (P = .03). In the asymptomatic group, adiponectin and NO levels showed elevations as compared with the symptomatic group but this increase was not significant (P > .05). Lipoprotein (a) and TNF-alpha levels acted inversely with adiponectin and NO. There was an insignificant decline in Lp(a) and TNF-alpha levels in the asymptomatic group as compared with the symptomatic group (P > .05).

Preliminary study showing the relationship between platelet fibronectin, sialic acid, and ADP-induced aggregation levels in coronary heart disease.

Several studies indicate that thrombosis plays an important role in the pathogenesis of coronary heart disease (CHD). Fibronectin is a multifunctional protein in plasma, other body fluids, and cell surface and plays an important role in platelet functions, including mediation of cell-cell and cell-surface interactions. Sialic acid is a regular constituent of glycoproteins and gangliozides in the outer cell membrane of mammalian cells. Therefore, the sialic acid content of platelets, which are characterized by their ability to aggregate with each other, can be important in leading to thrombus formation. In this study, platelet fibronectin, sialic acid-, and adenosine diphosphate (ADP)-induced platelet aggregation levels were determined in patients with CHD. Platelet sialic acid concentrations were determined by Warren's method. Platelet aggregation tests with ADP in platelet-rich plasma (PRP) were analyzed by use of an aggregometer. Platelet homogenate fibronectin levels were determined by ELISA. Total protein levels were determined by Lowry method. Our results indicate that, in patients with no vessel disease (patients with no obstructed vessel but suffering from chest pain, like angina pectoris) platelet fibronectin levels were significantly lower than the total of the other patients (patients with 1, 2, or 3 obstructed coronary vessels) (p<0.05). Sialic acid levels in patients with no vessel disease were significantly lower than the total of the patient group (p<0.05). There was significant (+) correlation between platelet aggregation, platelet fibronectin, platelet sialic acid, and severity of disease (p<0.05). Our preliminary findings suggest that, especially platelet fibronectin levels potentially represent a pathogenic factor for CHD.

Comparison of platelet fibronectin, ADP-induced platelet aggregation and serum total nitric oxide (NOx) levels in angiographically determined coronary artery disease.

INTRODUCTION: Coronary thrombosis is an important determinant of prognosis in patients with acute coronary syndromes. Fibronectin is also found in platelets within the alpha secretory granules and secreted following platelet stimulation by a variety of agonist. Available data suggest that expression of platelet fibronectin on the cell surface may indicate a role in platelet aggregation and adhesion to fibrin thrombi and connective tissue. Clear evidence has emerged that a concerted action of nitric oxide (NO) generated by either endothelial or platelet NO synthases regulates platelet activation, causing inhibition of adhesion and aggregation. The aim of the present study was determining and correlating the serum total NO (NOx), platelet fibronectin and ADP-induced platelet aggregation levels in coronary artery disease (CAD) patient subgroups. MATERIALS AND METHODS: A total of 43 coronary artery disease patients were included in this study. Peripheral blood samples from patients with coronary artery disease were obtained from the Department of Cardiology. Platelet aggregation tests with adenosine diphosphate (ADP) were analyzed by using aggregometer. Platelet fibronectin concentrations were determined by enzyme-linked immunosorbent assay (ELISA). Serum total nitric oxide (NOx) levels were determined by colorimetric method. RESULTS: In patients with double-vessel disease, platelet fibronectin levels were found to be significantly higher than no-vessel disease (p<0.001), single-vessel disease (p<0.01) and triple-vessel disease (p<0.001). In addition, in patients with single-vessel disease platelet fibronectin levels significantly higher than no-vessel disease (p<0.05). We could not find any significant differences in ADP-induced platelet aggregation and serum NOx values between CAD patient subgroups. There was a positive correlation between platelet fibronectin levels and severity of disease (r=0.315, p<0.05).

Evaluation of fibronectin, vitronectin, and leptin levels in coronary artery disease: impacts on thrombosis and thrombolysis.

In this study, the levels of fibronectin, vitronectin, leptin, tissue plasminogen activator (t-PA), and lipid parameters were investigated in patients with coronary artery disease (CAD) and control group. The average plasma fibronectin levels in CAD patients group were significantly higher compared with the control group (p=0.006). Moreover, in patients with triple-vessel disease, plasma fibronectin levels were found to be significantly higher than those in the control group (p<0.05). Plasma vitronectin levels in patients with CAD were found to be significantly higher than those in the control group (p=0.000). In addition, in patients with double vessel disease plasma vitronectin levels were significantly higher than no vessel disease and control group, triple vessel disease was significantly higher as compared with no vessel disease, single vessel disease, and control group (p<0.05). We could not find any significant differences in t-PA values between CAD patients and control group. On the other hand, the average leptin levels in the group of patients were higher than those in the control group but there were no statistically significant differences found between them (p>0.05) because of high SD values. There was strong (+) correlation between fibronectin, vitronectin, and severity of disease [vitronectin/severity of disease, r = 0.5074 (p = 0.000), fibronectin/severity of disease, r = 0.2971 (p = 0.007)]. In conclusion, we can say that fibronectin and vitronectin have become greatly important in pathogenesis of coronary artery disease. High leptin levels may be contribute to platelet aggregation in patients with coronary artery disease. But, elevated serum levels of leptin cannot be useful diagnostic and monitoring markers in patients with coronary artery disease.