Suleyman Yuce

Mean Platelet Volume and Vitamin D Level

BACKGROUND Vitamin D deficiency and a high mean platelet volume (MPV) are related to cardiovascular disease. We investigated whether vitamin D deficiency is associated with high MPV. METHODS This study included 434 patients without chronic disease who were not taking vitamin D or calcium supplements. Vitamin D was measured by chemiluminescent microparticle immunoassay on the Architect-I2000 system (Abbott Diagnostics, USA), and MPV was measured on the Cell-Dyn Ruby analyzer (Abbott Diagnostics). Patients were divided into Groups 1 (138 [men/women, 46/92]), 2 (148 [men/women, 54/94]), and 3 (148 [men/women, 50/98]) according to vitamin D levels of <10 ng/mL, 10-20 ng/mL, and >20 ng/mL, respectively. RESULTS The vitamin D level in Group 1 (7.7±1.9 ng/mL) was lower than that in Group 2 (15.1±1.6 ng/mL, P<0.001) and Group 3 (25.6±6.3 ng/mL, P<0.001). The MPV in Group 3 (7.5±1.0 fL) was lower than that in Group 1 (8.1±1.1 fL, P<0.001) and Group 2 (7.9±1.0 fL, P=0.009). Linear regression analysis showed that low levels of vitamin D (β=-0.109, P=0.019) was independently associated with increased MPV. CONCLUSIONS There was a strong association between a low vitamin D level and a high MPV; therefore, vitamin D deficiency may be associated with increased MPV.

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 effect of Gilbert's syndrome on the dispersions of QT interval and P-wave: an observational study.

OBJECTIVE Gilberts syndrome (GS) decreases the incidence of atherosclerotic heart disease. The aim of the study was to evaluate whether the arrhythmia risk markers such as P-wave dispersion (Pd), QT dispersion (QTd) are reduced in patients with GS compared with healthy subjects. METHODS Sixty-one patients diagnosed with GS (31 females, 30 males) who had applied to the internal medicine outpatient clinic in the hospital were included in this cross-sectional, observational study. A control group of 61 healthy persons (31 females, 30 males), who were non-smokers and drinkers, were included. Both groups were between 16-45 years old. Results of anthropometric measurements, laboratory assays and electrocardiographic findings were recorded for each participant. Independent sample t-test and nested ANOVA were used for data analysis. RESULTS In the GS group were Pd value 36±16.7 msec, QTd 48.7±10.7 msec and heart rate (HR) 74±8 beat/min. In the control group were Pd 51±28 msec, QTd 53±12 msec and HR 78±10 beat/min. The Pd of patients group (p<0.001), QTd (p=0.038) and HR (p=0.021) were significantly lower than the control group. CONCLUSION According to our studys results, in these patients, increased bilirubin levels are associated with decrease in HR, Pd and QTd, which consequently might decrease the incidence of cardiac arrhythmias and coronary artery disease. Further studies are needed to clarify the protective role of bilirubin in risk of arrhythmias in this category of patients.

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.

Protective effect of infliximab on methotrexate-induced liver injury in rats: unexpected drug interaction.

AIMS Although methotrexate (mtx) is a widely used agent to treat cancer and inflammatory diseases, its hepatotoxic effect limits for clinical utility. We aimed to investigate whether infliximab (inf), an inhibitor of tumor necrosis factor-alpha (TNF-α) has a protective effect against mtx-induced hepatotoxicity. MATERIALS AND METHODS For mtx group, the animals received an intraperitoneal single dose injection of mtx at a dose of 20 mg/kg. For inf group, the animals received an intraperitoneal single dose injection of inf at a dose of 7 mg/kg. For mtx + inf group, the single dose of inf at a dose of 7 mg/kg was given 72 h prior to mtx injection. After 72 h, a single dose of mtx 20 mg/kg was given. All rats were sacrificed 5 days after mtx injection. RESULTS TNF-α and nitric oxide (NO) levels of mtx group was significantly higher than the control (P < 0.001), inf (P < 0.001) and mtx + inf (P < 0.001) groups. Total score of histological damage was higher in the mtx group when compared with the mtx + inf group. Arginase and carbamoyl phosphate synthetase 1 (CPS-1) of mtx group was suppressed in comparison with the control group and was markedly increased in mtx + inf group. CONCLUSION Inf may partially prevent mtx-induced hepatic damage in rats. However, the combined usage of mtx and inf increases arginase and CPS-1 enzyme activities and at the same time blocks TNF-α. This combination especially in cancer patients may lead to cancer cell invasion and metastasis.

Topiramate ameliorates abdominal aorta cross-clamping induced liver injury in rats.

Background and Aim: Ischemia/reperfusion (I/R) injury in the liver occurs after a prolonged period of ischemia followed by restoration of hepatic blood perfusion. During the surgery of abdominal aorta, I/R injury causes damage to lower extremities and many organs, especially liver. The antioxidant and tumor necrosis factor-alpha (TNF-α) suppression effects of topiramate (TPM) have been reported in several studies. We evaluated the potential protective effect of TPM on cellular damage in liver tissue during I/R injury. Materials and Methods: Thirty male Wistar albino rats were divided into three groups: Control, I/R, and I/R plus TPM (I/R + TPM) groups. Laparotomy without I/R injury was performed in the control group. After laparotomy, cross-ligation of infrarenal abdominal aorta was applied for 2 h in I/R groups that was followed by 2 h of reperfusion. TPM (100 mg/kg/day) was orally administrated to the animals in the I/R + TPM group for seven consecutive days before I/R procedure. Results: The I/R groups TNF-α and interleukin-6 (IL-6) levels were significantly higher than those of the control (P = 0.010; P = 0.002) and I/R + TPM groups (P = 0.010; P = 0.002, respectively). Asymmetric dimethyl arginine (ADMA) levels of I/R group were higher than the control (P = 0.015) and I/R + TPM groups. I/R caused serious histopathological damage to liver tissue; however, TPM led to very low histopathological changes. Conclusion: Our data demonstrated that TPM treatment prominently decreases the severity of liver I/R injury. TPM pretreatment may have preventive effects on liver injury via I/R during intra-abdominal surgery.

Somatostatin receptor 2 and 5 expressions in gastroenteropancreatic neuroendocrine tumors in Turkey.

BACKGROUND Gastroenteropancreatic neuroendocrine tumors (GNs) are slow growing and although their incidence has increased in recent years, they are relatively rarely seen. Somatostatin analogues are used in the treatment of GNs that express somatostatin receptor (SR). We aimed to investigate the expression of SR2 and SR5 in GNs. MATERIALS AND METHODS In this study the expression of SR2 and SR5 was investigated immunohistochemically in 49 cases (26 males, 23 females) diagnosed and graded with GN according to the World Health Organization classification 2010. RESULTS The percentage of SR2 staining was 91.0% in grade 1, 82.8% in grade 2 and 100% in grade 3. On the other hand, the percentage of SR5 staining was 81.8% % in grade 1, 60.0% in grade 2 and 0% in grade 3. According to the tumor localization, the percentages of SR2 expression were as follows: pancreas 85.7%, stomach 100%, small bowel 70%, appendix 85.7% and rectum 100%. The percentages of SR5 expression were: pancreas 61,9%, stomach 37.5%, small bowel 70%, appendix 71.5% and rectum 66.6%. There was a significant negative correlation between ki67 percentage and SR5 expression (r=-0.341, p=0.016). CONCLUSIONS In this study, GNs were found to highly express SR2 and SR5. Although the expression of SR2 and SR5 changed according to tumor localization, the expression of SR2 was higher than the expression of SR5 in GN. There was a significant negative correlation between ki67 and SR5. Accordingly, SR5 may be a prognostic indicator of GN.

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.