Aynur Kırbaş

Low-density lipoprotein subfraction, carotid artery intima-media thickness, nitric oxide, and tumor necrosis factor alpha are associated with newly diagnosed ischemic stroke.

Objectives: Small dense (sd) low-density lipoprotein (LDL), tumor necrosis factor (TNF) alpha (α), and nitric oxide (NO) have recently emerged as important stroke risk factors. The aim of the study was to investigate the effects of increased levels of small LDL particle size, TNF-α and NO on the developed ischemic stroke and increased carotid artery intima-media thickness (CIMT). Materials and Methods: A total of 29 women and 25 men (a total of 54 ischemic stroke patients) and a similar age group of 50 controls (29 females and 21 males) were included in the study. CIMT, C-reactive protein (CRP), TNF-α, NO, and lipid subfraction test of the two groups were measured. Results: The mean LDL particle size was smaller in patients with stroke than in the controls (26.8 ± 0.31 nm vs. 27.0 ± 0.31 nm, P = 0.003). sd-LDL, TNF-α, NO, CRP, right CIMT, and left CIMT were higher in patients with stroke than in the controls (respectively; 8.2 ± 7.8 mg/dL vs. 3.3 ± 3.5 mg/dL, P < 0.001;75.6 ± 25.0 pg/mL vs. 65.4 ± 9.1 pg/mL, P = 0.009;76.4 ± 53.3 mmol/L vs. 41.5 ± 27.0 mmol/L, P < 0.001;1.9 ± 2.6 mm vs. 0.4 ± 0.3 mm P < 0.001;0.97 ± 0.38 mm vs. 0.83 ± 0.15 mm, P = 0.007;1.04 ± 0.44 mm vs. 0.87 ± 0.19 mm, P = 0.010). Conclusion: These results show that sd-LDL is independently associated with the incidence of stroke and may be a risk factor in the development of stroke. In addition, TNF-α, NO, right CIMT, and left CIMT may be a risk factor in the development of ischemic stroke.

The effects of Gilbert's syndrome on the mean platelet volume and other hematological parameters.

The protective effect of increased levels of indirect bilirubin on atherosclerotic heart disease in patients of Gilberts syndrome is well known. The aim of the study was to investigate the effects of increased levels of bilirubin on the mean platelet volume (MPV) and other hematological parameters. Thirty-two men and 36 women (a total of 68 Gilberts syndrome patients) and a similar age group of 68 healthy individuals (32 men and 36 women) were included in the study. Hematologic tests, C-reactive protein (CRP) and biochemical values of the two groups were checked. MPV level of Gilberts syndrome group was 7.8 ± 1.0 fl and CRP 0.2 ± 0.27 mg/dl. In the control group MPV was 8.6 ± 1.0 fl and CRP 0.3 ± 0.38 mg/dl. MPV of patients group (P < 0.001) and CRP (P = 0.037) were significantly lower than the control group. When dividing Gilberts syndrome and control groups according to sex into subgroups the level of indirect bilirubin in men with Gilberts syndrome (1.8 ± 0.8 mg/dl) was found to be higher than other groups. Healthy men had higher levels of MPV (8.8 ± 0.9 fl) whereas Gilberts syndrome male patients had lower levels (7.7 ± 1.1 fl), (P < 0.001). The elevated levels of bilirubin and decreasing levels of MPV and CRP in Gilberts syndrome patients may have an effect on the slowing down of the atherosclerotic process.

The relationship of plasma catestatin concentrations with metabolic and vascular parameters in untreated hypertensive patients: Influence on high-density lipoprotein cholesterol

Objective: Catestatin has several cardiovascular actions, in addition to diminished sympatho-adrenal flow. Decreased plasma catestatin levels may reflect a predisposition for the development of hypertension and metabolic disorders. We planned to investigate the possible roles of catestatin in untreated hypertensive patients. As a secondary objective, we compared catestatin concentrations of healthy subjects with those of hypertensive patients in order to understand whether catestatin is increased reactively or diminished at onset. Methods: Our study was cross-sectional and observational. The patient group, comprising 109 consecutive untreated hypertensive patients without additional systemic or coronary heart disease, underwent evaluations of plasma catestatin, waist circumference, lipid parameters, left ventricular mass, carotid intima-media thickness, and flow-mediated dilation of the brachial artery. Additionally, we measured catestatin concentrations of 38 apparently healthy subjects without any disease using a commercial enzyme-linked immunosorbent assay kit. Results: We documented increased catestatin concentrations in previously untreated hypertensive patients compared to healthy controls (2.27±0.83 vs. 1.92±0.49 ng/mL, p=0.004). However, this association became insignificant after adjustments for age, gender, height, and weight. Within the patient group, catestatin levels were significantly higher in females. Among all study parameters, age, high-density lipoprotein cholesterol (HDL-C) correlated positively to plasma catestatin, whereas triglycerides, hemoglobin, and left ventricular mass correlated negatively to plasma catestatin. We could not detect an association between vascular parameters and catestatin. Catestatin levels were significantly elevated with increasing HDL-C (1.91±0.37, 2.26±0.79, and 3.1±1.23 ng/mL in patients with HDL-C <40, 40-60, and >60 mg/dL, respectively). Multiple linear regression analysis revealed age (beta: 0.201, p=0.041) and HDL-C (beta: 0.390, p<0.001) as independent correlates of plasma catestatin concentration. Additionally, male gender (beta:-0.330, p=0.001) and plasma catestatin (beta: 0.299, p=0.002) were significantly associated with HDL-C concentrations. Conclusion: We documented that plasma catestatin is an independent predictor of high-density lipoprotein cholesterol. In addition to antihypertensive effects, catestatin appears to be related to improved lipid and metabolic profiles. Coexistence of low catestatin levels with low HDL-C may provide a probable mechanism for the predictive value of low HDL-C for increased hypertension and cardiovascular events.

Adalimumab Ameliorates Abdominal Aorta Cross Clamping Which Induced Liver Injury in Rats

The aim of this study was to investigate the possible protective effects of adalimumab (ADA) on cell damage in rat liver tissue during ischemia/reperfusion (I/R) injury of infrarenal abdominal aorta. Thirty male Wistar-albino rats were divided into three groups: control, I/R, and I/R+ADA, each group containing 10 animals. Laparotomy without I/R injury was performed in the control group animals. Laparotomy in the I/R group was followed by two hours of infrarenal abdominal aortic cross ligation and then two hours of reperfusion. ADA (50 mg/kg) was administered intraperitoneally as a single dose, to the I/R+ADA group, five days before I/R. The tumor necrosis factor-alpha (TNF-α) (pg/mg protein) and nitric oxide (NO) (µmol/g protein) levels in the I/R group (430.8 ± 70.1, 8.0 ± 1.1, resp.) were significantly higher than those in the I/R+ADA group (338.0 ± 71.6, P = 0.006; 6.3 ± 1.2, P = 0.008) and the control group (345.5 ± 53.3, P = 0.008; 6.5 ± 1.5, P = 0.010, resp.). I/R causes severe histopathological injury to the liver tissue, but ADA leads to much less histopathological changes. ADA treatment significantly decreased the severity of liver I/R injury. ADA pretreatment may have protective effects on experimental liver injury.

The evaluation of relationship between adiponectin levels and epicardial adipose tissue thickness with low cardiac risk in Gilbert`s syndrome: an observational study.

OBJECTIVE Atherosclerotic heart diseases are less frequently seen in patients with Gilberts syndrome (GS). We aimed to investigate whether serum adiponectin (APN) and epicardial adipose tissue (EAT) thickness have an effect beside the antioxidant effect of bilirubin in lowering the incidence of the atherosclerotic process. METHODS Sixty-eight patients diagnosed with GS (39 females and 29 males) who had applied at the internal medicine clinic of the hospital were included in this cross-sectional, observational study. The control group included 63 healthy people (39 females and 24 males). EAT thickness was measured by echocardiography. The serum APN levels were also checked. Statistical analysis was performed by using independent sample t-test, Pearson correlation and linear regression analyses. RESULTS The mean age of the GS group was 28 ± 9 years, and the average EAT thickness was found to be 2.5 ± 0.1 mm. The mean age of the control group was 26 ± 6 years, and the average EAT thickness was found to be 4.2 ± 0.5 mm. When comparing the two groups, the EAT thickness of the GS group was found to be significantly lower (p<0.001) than that of the control group. In the GS group the APN was 14.9 ± 4.2 mg/L, and in the control group the APN was 12.6 ± 4.5 mg/L (p<0.022). We found that total bilirubin (β=-1,607, p<0,001) and indirect bilirubin (β=1,086, p<0,001) have an independent association with decreased EAT thickness. CONCLUSION EAT thickness is associated with coronary atherosclerosis. Low EAT thickness may be related with low release of proinflammatory cytokine. High levels of APN may be related high anti-inflammatory effect. Therefore, low EAT thickness and high levels of APN may demonstrate protective effect on atherosclerotic heart diseases in GS patients.

Increased YKL-40 levels in patients with isolated coronary artery ectasia: an observational study

OBJECTIVE YKL-40, a new biomarker of localized inflammation, is secreted by macrophages within the atherosclerotic plaques. Coronary artery ectasia (CAE) is a clinical entity with unclear etiopathogenesis. Some studies have revealed that CAE may be a form of atherosclerosis that has more localized and intense inflammatory properties than atherosclerosis. The goal of this study was to investigate YKL-40 and C-reactive protein (CRP) levels in patients with isolated CAE compared to patients with normal coronary arteries (NCA) and coronary artery disease (CAD). METHODS Our study has an observational and cross-sectional design. Forty-nine patients with isolated CAE (mean age: 60±10 years), 30 age-and gender-matched control participants with NCA (30 patients, mean age: 58±12 years) and 30 patients with CAD (mean age: 61±10 years), were included in the study. The relationship between YKL-40, CRP levels and the presence of CAE was investigated. Univariate and multiple logistic regression analysis were used for analysis of independent variables to predict CAE. RESULTS Serum YKL-40 levels were significantly different among study groups (NCA: 110±53 μg/L, CAE: 144±68 and CAD: 180±117, p=0.005). CAD group and CAE group had significantly higher YKL-40 levels than NCA group (p=0.004 and p=0.015, respectively). CRP was not significantly different between three groups. In addition, there were no any statistically significant differences, with respect to age, gender, the presence of hypertension or diabetes mellitus, and the smoking status (p>0.05). Logistic regression analysis revealed only YKL-40 level as the determinant of CAE (OR: 1.010, 95% CI: 1.001-1.019, p=0.027). CONCLUSION YKL-40 levels in patients with isolated CAE compared to patients with NCA were found significantly high and only YKL-40 level was established as the determinant of CAE. We believe that further studies are needed to clarify the possible causative roles of YKL-40 in patients with isolated CAE.

Requests for Tumor Marker Tests in Turkey Without Indications and Frequency of Elevation in Benign Conditions

AIMS To investigate the incidence of ordering tests for tumor markers which are used in cancer diagnosis, follow-up treatment and detection of recurrence, the rate of elevation in benign diseases and which clinics order them frequently. MATERIALS AND METHOD Data for the tumor markers carbohydrate antigen 19-9 (CA 19-9), carcinoembryonic antigen (CEA), cancer antigen 125 (CA 125), cancer antigen 15-3 (CA 15-3) and alpha- fetoprotein (AFP) that were ordered by all the clinics in our Hospital between 2010 and 2011 were screened. When excluding repeated orders the results of 3,416 patients were available. It has been determined that in which benign diseases were the tumor markers frequently ordered and which of these conditions had high levels of them. RESULTS CA 19-9 was ordered for 1,858 patients 191 (10.3%) were malignant while 1667 (89.7%) were ordered in benign diseases. For CEA the total was 1,710, 226 (13.2%) malignant and 1484 (86.8%) benign, and for CA 125 1267, 111 (8.8%) malignant and 1156 (91.2%) benign. AFP was ordered for 1687 cases, 80 (4.7%) malignant but 1607 (95.3%) benign. CA 15-3 was ordered 1449 times, 174 (12%) for malignant and 1275 (88%) for benign diseases. In all cases, considerable proportions were positive. CONCLUSIONS It was shown that clinicians frequently order tumor markers for benign conditions. The findings of this study has shown that tumor markers are used widely without indications as cancer screening tests.

The Protective Effect of Adalimumab on Renal Injury in a Model of Abdominal Aorta Cross-Clamping

BACKGROUND Adalimumab (ADA) is a potent inhibitor of tumor necrosis factor (TNF-α). ADA treatment suppresses proinflammatory cytokines, leading to a decrease or inhibition of the inflammatory process. OBJECTIVES The aim of this study was to investigate the possible protective effects of ADA on oxidative stress and cellular damage on rat kidney tissue after ischemia/reperfusion (I/R). MATERIAL AND METHODS A total of 30 male Wistar albino rats were divided into three groups: control, I/R, and I/R plus ADA (I/R + ADA); each group comprised 10 animals. The control group underwent laparotomy without I/R injury. After undergoing laparotomy, I/R groups underwent two hours of infrarenal abdominal aortic cross ligation, which was followed by two hours of reperfusion. ADA (50 mg/kg) was administered as a single dose, intraperitoneally, to the I/R + ADA group, 5 days before I/R. RESULTS The I/R groups TNF-α (1150.9 ± 145.6 pg/mg protein), IL-1β (287.0 ± 32.4 pg/mg protein) and IL-6 (1085.6 ± 56.7 pg/mg protein) levels were significantly higher than those of the control (916.1 ± 88.7 pg/mg protein, p = 0.003; 187.5 ± 37.2 pg/mg protein, p < 0.001; 881.4 ± 57.1 pg/mg protein, p < 0.001, respectively) and I/R + ADA groups (864.2 ± 169.4 pg/mg protein, p = 0.003; 241.4 ± 33.4 pg/mg protein, p = 0.010; 987.7 ± 66.5 pg/mg protein, p = 0.004, respectively). To date, a few histopathological changes have been reported regarding renal I/R injury in rats due to ADA treatment whereas I/R caused severe histopathological injury to kidney tissue. CONCLUSIONS ADA treatment significantly attenuated the severity of kidney I/R injury, inhibiting I/R-induced oxidative stress and renal damage. Because of its anti-inflammatory and antioxidant effects, ADA pretreatment may have protective effects on experimental kidney injury.

Effects of lisinopril on NMDA receptor subunits 2A and 2B levels in the hippocampus of rats with l-NAME-induced hypertension

Hypertension is major risk factor leading to cerebrovascular pathologies. N-methyl d-aspartate receptors (NMDARs) and renin-angiotensin system are involved in neuronal plasticity, as well as cognitive functions in the hippocampus. In this study, we examined the effects of lisinopril, an ACE inhibitor, on the levels of hippocampal NMDAR subunits; NR2A and NR2B in l-NAME (Nϵ-nitro-l-arginine Methyl Ester)-induced hypertensive rats. In addition, malondialdehyde (MDA) levels were measured as a marker for lipid peroxidation. Compared with the control group, the MDA level was significantly increased after 8 weeks in the l-NAME-treated group. Rats treated with lisinopril and l-NAME plus lisinopril were found to have significantly decreased hippocampal MDA levels. Regarding the hippocampal concentrations of NR2A and NR2B, there were no statistically significant differences between groups. We demonstrated that lisinopril treatment has no direct regulatory effect on the levels of NR2A and NR2B in the rat hippocampus. Our results showed that Lisinopril could act as an antioxidant agent against hypertension-induced oxidative stress in rat hippocampus. The findings support that the use of lisinopril may offer a good alternative in the treatment of hypertension by reducing not only blood pressure but also prevent hypertensive complications in the brain.

Response to a Letter to the Editor Entitled “Low Serum B12 Level Does Not Mean Vit. B12 Deficiency-Problems Related to the Diagnosis of Vitamin B12 Deficiency”

We thank Dr Grzybowski for the interest he has shown in our article entitled ‘‘Evaluation of peripapillary retinal nerve fiber layer thickness in patients with vitamin B12 deficiency using spectral domain optical coherence tomography’’. Firstly, Dr Grzybowski argues that low serum vitamin B12 level is not automatically diagnostic for vitamin B12 deficiency in asymptomatic, hematologically normal patients. He states that the clinical picture is crucial for determination of the vitamin B12 deficiency. In addition, he says that the levels of the other biomarkers such as methylmalonic acid or homocysteine could be used for the diagnosis. In our study, we used serum vitamin B12 levels, clinico-electrophysiological evaluation and spinal magnetic resonance imaging for the diagnosis of vitamin B12 deficiency and related neuropathies. Eight patients had clinical vitamin B12 deficiency. However, the rest of the patients (37 patients) had subclinical cobalamin deficiency (SCCD). They were hematologically normal patients and they had no clinical signs except for the low serum vitamin B12 levels. It is known that the anemia is not seen in the SCCD. Biochemical markers of cobalamin status have largely confirmatory roles in the diagnosis of clinical deficiency of vitamin B12, whose clinical expressions provide the diagnostic quasi-gold standard. Cobalamin measurement is generally sufficient for the diagnosis because it has more than 90–95% sensitivity in the clinical deficiency. On the other hand, the diagnosis of SCCD depends completely on metabolic testing because the patients are clinically normal. However, the optimal testing for diagnosis of SCCD continues to be investigated. As recently reported, all biomarkers can produce falsely abnormal results, and none is a diagnostic gold standard. Secondly, Dr Grzybowski points out that the reason for vitamin B12 deficiency in our patients was not given and intrinsic factor (IF)-related malabsorption was not verified. The cause of vitamin B12 deficiency and IF was not evaluated in our work because it has been shown that the causes of SCCD are unknown in more than 60% of cases. As Dr Grzybowski states, there are some problems with the diagnosis of vitamin B12 diagnosis. He has enriched our article by discussing these problems throughout his letter. We, sincerely thank him for his contribution to our work.