Firat Bayraktar

The Levels of Soluble CD40 Ligand and C-Reactive Protein in Normal Weight, Overweight and Obese People

Objective: Obesity has been suggested as an independent risk factor for cardiovascular disease. Increasing evidence shows that engagement of soluble CD40 ligand (sCD40L) with its receptor plays a crucial role in the pathogenesis of atherosclerosis. The aim of the present study was to test whether obesity is associated with low-grade systemic inflammation as measured by serum high-sensitive C-reactive protein (hsCRP) and sCD40L concentration. Methods: Serum hsCRP and sCD40L concentrations were measured in 148 nondiabetic people. The participants were divided into three groups depending upon their body mass index (BMI) levels: Group 1 (normal weight), BMI<25 kg/m2; Group 2 (overweight), BMI 25 kg/m2 to 29.9 kg/m2; and Group 3 (obese), BMI≥30 kg/m2. Results: Obese people had more elevated hsCRP levels than both their normal weight and overweight counterparts (P=0.000 and P=0.000, respectively). Similarly, serum concentrations of sCD40L were significantly higher, statistically, in obese subjects compared with normal weight subjects (P=0.003). In addition, obese subjects had higher values of sCD40L than overweight subjects, but the difference did not reach statistical significance (P=0.063). The levels of high-density lipoprotein cholesterol were significantly lower in obese subjects compared to normal weight subjects (P=0.048). The analysis of platelet count disclosed a statistically significant difference between obese subjects and normal weight subjects (P=0.028). The levels of BMI were positively correlated with the serum levels of hsCRP and sCD40L in all subjects (r=0.514, P=0.000 and r=0.283, P=0.000, respectively). Levels of hsCRP were positively correlated with waist circumference, fasting glucose, total cholesterol, triglyceride, low-density lipoprotein cholesterol, leukocytes, platelets, systolic and diastolic blood pressure. Similarly, soluble CD40L levels were positively correlated with waist circumference, fasting glucose and leukocytes. Conclusion: Obese patients showed a significant increase of hsCRP and sCD40L levels compared with normal weight subjects, which might contribute to the known proinflammatory milieu found in these patients.

The Effects of Estrogen and Raloxifene Treatment on Antioxidant Enzymes in Brain and Liver of Ovarectomized Female Rats

Recent studies documented that estrogen have antioxidant properties in‐vitro, there are conflicting results on the effect of estrogen in vivo. We aimed to investigate the effects of estradiol and Raloxifene on the antioxidant enzyme [superoxide dismutase (SOD) and catalase (CAT)] activities and MDA levels in brain and liver homogenates of ovariectomized female rats. Twelve weeks after ovariectomy, female Sprague–Dawley rats (n = 26) were divided into three groups: (1) Ovariectomized placebo group (n = 6) was given physiologic saline. (2) Estrogen group (n = 10) was given Ethynyl estradiol, 0.1 mg/kg sc. (3) Raloxifene group (n = 10) was given raloxifene, 1 mg/kg sc during 8 weeks. Ten rats were used as naive controls without any treatment (Sham operated group, n = 10). Ovariectomy lead to an increase in the CAT activities in liver tissue samples compared to the sham group ( p = 0.056, Mann–Whitney test). While estrogen treatment reversed to normal levels of CAT activities, raloxifene remained as ineffective. Superoxide dismutase activities and MDA levels in liver were remained unchanged in all groups. There was no significant change in the brain tissue SOD and CAT activities between the control, ovariectomy, estrogen treated, and raloxifen treated groups. We determined an increase in MDA levels in brain of ovariectomised rat ( p = 0.02). While raloxifene treatment reversed to normal levels of MDA ( p = 0.008), estrogen treatment failed. Our data showed that estrogen may play a role in regulation of CAT and SOD activities in liver due to its antioxidative effects. We can suggest that estrogen and raloxifene exert their antioxidative effects in brain rather than liver. Since Raloxifenes effect is more clear than estradiol, raloxifene may be suggested primarily for treatment and/or prevention of diseases which can be resulted from oxidative stress in postmenopausal women.

Effect of surgical weight loss on free radical and antioxidant balance: a preliminary report.

Background:This study observes the effect of surgical weight loss on free radical and antioxidant vitamin balance. Patients and Methods: 22 consecutive morbidly obese patients undergoing vertical banded gastroplasty (VBG) were chosen for the study. Postoperative studies were done at 12 and 24 weeks. Plasma antioxidant and vitamin determinations were performed by HPLC method. Results: Subjects lost a significant amount of weight (P<0.01). Compared to preoperative measurements, postoperative measurements of plasma betacarotene were not statististically different both at 12 and 24 weeks (13.86±1.26 μg/dl, 12.35±1.2, P=0.44; 14.33±2.03, P=0.77; preoperatively, 12 and 24 weeks respectively). Alpha-tocopherol increased slightly at the 12th week; the difference was not significant (8.50±0.77; 9.56±0.82, P=0.37; preoperatively and 12th week respectively). The levels of alpha-tocopherol rose at 24th week significantly (10.89±0.55, P=0.028). The indicator of lipid peroxidation (malondialdehyde) decreased with weight loss (1.505±0.11 μmol/L preoperatively; 0.75±0.062 at 12th week, P=0.01; 0.712±0.05 at 24th week, P<0.01). Conclusion: Our data show that free radical generation falls markedly in association with weight loss after VBG. Surgical weight loss leads to significant decrease in oxidant production and also leads to increase in some antioxidant vitamins. The demon stration of decreased free radical generation and correction of balance between free radicals and antioxidant vitamins has important implications for oxidative mechanisms underlying obesity-associated disorders.

Enhanced levels of soluble CD40 ligand and C-reactive protein in a total of 312 patients with metabolic syndrome

The metabolic syndrome (MS) is associated with a systemic inflammatory response that plays an important pathogenetic role in atherothrombotic disease. Increasing evidence indicates that CD40-CD40 ligand interactions constitute an important mediator for vascular inflammation. The purpose of this study was to assess whether high-sensitivity C-reactive protein (hs-CRP) and soluble CD40 ligand (sCD40L) levels were increased in patients with MS. During the study period from January 2004 to August 2004, 312 patients with MS and 98 control subjects were included. Anthropometric measurements, blood pressure assessment, electrocardiography, and blood measurements including fasting blood glucose, postprandial blood glucose, total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, triglyceride, glycated hemoglobin, white blood cell (WBC), platelets, hs-CRP, and sCD40L were performed. Patients with MS were divided into 3 groups based upon their glucose tolerance (group 1, normal glucose tolerance; group 2, prediabetic group; and group 3, diabetes mellitus). Patients with MS showed a significant increase of WBC, hs-CRP, and sCD40L levels compared with control subjects. The levels of both hs-CRP and sCD40L were positively correlated with body mass index (BMI). High-sensitivity CRP levels were also positively correlated with waist circumferences, fasting blood glucose, postprandial blood glucose, and glycated hemoglobin, and negatively correlated with high-density lipoprotein cholesterol. In patients with MS, both hs-CRP and sCD40L levels were positively correlated with WBC count. We found a positive correlation between sCD40L and platelets. Among the subgroups of patients with MS, the mean levels of WBC, hs-CRP, and sCD40L did not show any significant differences. In conclusion, elevated levels of WBC, hs-CRP, and sCD40L in MS patients provide further insight into the relationship between MS and inflammation. In our study, positive correlations between BMI and both hs-CRP and sCD40L levels suggest that BMI is an important determinant of a chronic inflammatory state in patients with MS. Moreover, this study reports significantly increased levels of WBC, hs-CRP, and sCD40L not only in diabetic subjects with MS but also in prediabetic subjects and nondiabetic subjects with MS compared with control subjects. Our data suggest that MS patients have proinflammatory state independent of their glucose tolerance status. In our study, the positive correlation between the levels of sCD40L and platelets in patients with MS supports previous reports indicating that sCD40L are derived predominantly from platelets.

Allergic reactions to human insulin: a review of current knowledge and treatment options

Although the incidence of insulin allergy decreased after the introduction of recombinant human insulin preparations, it is still a major problem which may be life-threatening in some cases. In this article, we attempted to review current knowledge concerning allergic reactions to human insulin and discuss the available treatment options of insulin allergy.

Hashimoto's Thyroiditis, but not Treatment of Hypothyroidism, Is Associated with Altered TGF-β1 Levels

BACKGROUND Although the role of cytokines in the development of Hashimotos thyroiditis has already been established, its pathogenesis has not yet been clearly elucidated. The aim of our study was to investigate serum transforming growth factor-beta1 (TGF-beta1) levels in patients with Hashimotos thyroiditis as well as the effect of achieving euthyroidism by levothyroxine replacement on TGF-beta1 levels. METHODS Twenty nine female, newly diagnosed hypothyroid Hashimotos thyroiditis patients (16 overt, 13 subclinical hypothyroid) and 25 age- and sex-matched healthy controls were enrolled in the study. RESULTS Serum TGF-beta1 levels were lower in the Hashimotos thyroiditis group when compared with control cases. Although significant differences were noted in lipid levels and in anthropometric measurements following levothyroxine replacement, serum TGF-beta1 levels remained unchanged. CONCLUSIONS Our data suggest that altered TGF-beta1 levels are associated with the presence of Hashimotos thyroiditis, not with the treatment of thyroid dysfunction. Autoimmunity may have been triggered as a result of decreased immunosuppressive effect induced by depressed TGF-beta1 levels in patients with Hashimotos thyroiditis.

Plasma Thiobarbituric Acid-Reactive Substance Levels in Subclinical Hypothyroidism

Objective: The purpose of this study was to determine thiobarbituric acid-reactive substance (TBARS) levels in subclinical hypothyroidism and to examine the effect of levothyroxine replacement on TBARS levels. Subjects and Methods: A cohort of 28 female patients with subclinical hypothyroidism and 24 healthy controls were enrolled in this study. The levels of plasma TBARS, serum lipids, and high-sensitive C-reactive protein (CRP) in patients with subclinical hypothyroidism at baseline and after achieving euthyroid state by levothyroxine were assessed. Results: TBARS levels of the patients were similar to those of the control group in the subclinical hypothyroid state and after restoration of euthyroidism by levothyroxine replacement. TBARS levels decreased after levothyroxine treatment, but did not reach statistical significance. There was no significant correlation between TBARS, lipid and CRP levels. Serum CRP levels were higher in subclinical hypothyroidism (4.28 ± 0.9 mg/l) than in the control group (1.95 ± 0.34 mg/l) and the difference was statistically significant (p = 0.03). After achieving euthyroid state, CRP levels decreased significantly in patients with subclinical hypothyroidism from 4.28 ± 0.9 to 2.32 ± 0.6 mg/l (p = 0.006). Conclusion: Our findings suggest that there is no significant alteration of plasma TBARS levels neither in subclinical hypothyroid state nor after achieving euthyroid state. Serum CRP level is higher in patients with subclinical hypothyroidism than in the control group. Normalization of thyroid state seems to effectively reduce serum CRP levels in subclinical hypothyroidism without any correlation with TBARS activity.

Long-term treatment with acarbose for the treatment of reactive hypoglycemia

Objective: Acarbose, a potent alpha-glucosidase inhibitor, provides a new concept for the treatment of metabolic disorders, and particularly diabetes mellitus. It reduces the postprandial blood glucose increment and insulin response. For this reason the drug has been successfully used not only in the treatment of type 1 and type 2 diabetes, but also in the management of reactive hypoglycemia and dumping syndrome. The primary aim of the present study is to evaluate the long-term effect of acarbose in reducing hypoglycemic symptoms and influencing laboratory measurements in patients with the diagnosis of reactive hypoglycemia. Design and Methods: 21 non-obese (BMI <27 kg/m2) patients (6 males, 15 females) complaining of postprandial symptoms suggesting hypoglycemia and who showed blood glucose values of <54 mg/dI on one or more occasions during a 5 h oral glucose tolerance test (OGTT) were selected. Results: Before treatment, ingestion of glucose decreased plasma glucose levels at the 3rd and 4th hours, the lowest levels being 39 mg/dl and 45 mg/dl respectively. Eighteen patients had hypoglycemic symptoms during OGTT. Following 3 months of acarbose treatment, the lowest plasma glucose levels at the 3rd and 4th hours increased to 67 mg/dI and 75 mg/dI respectively. Plasma insulin and c-peptide levels were reduced between the 1st and 5th hours, but only the 1st and 2nd hour decrements were statistically significant. The area under the curve (AUC) between 0–300 minutes for insulin was not significant. Plasma glucose levels were significantly increased during the last 3 hours The AUC for glucose was not significantly changed. Frequency of hypoglycemic attacks was reduced from 4 times a week to 1. C-peptide levels in 24-hour urine collection did not change significantly: 45 μg/I and 56 μg/I respectively before and after treatment. Conclusions: These results confirm that acarbose may be of value in preventing reactive hypoglycemia by reducing the early hyperglycemic stimulus to insulin secretion, and in the treatment of reactive hypoglycemia.

Acute phase reactants predict the risk of amputation in diabetic foot infection.

BACKGROUND prediction of amputation would aid clinicians in the management of diabetic foot infections. We aimed to assess the predictive value of baseline and post-treatment levels of acute phase reactants in the outcome of patients with diabetic foot infections. METHODS we collected data prospectively during minimum follow-up of 6 months in patients with infected diabetic foot ulcers hospitalized in Dokuz Eylul University Hospital between January 1, 2003, and January 1, 2008. After excluding patients who did not attend the hospital for follow-up visits regularly (n = 36), we analyzed data from 165 foot ulcer episodes. RESULTS limb ischemia and osteomyelitis were much more frequent in patients who underwent amputation. Wagner grade, which assesses ulcer depth and the presence of osteomyelitis or gangrene, was higher in patients who needed amputation. Ulcer size was slightly larger in the amputation group. Baseline and post-treatment C-reactive protein levels, erythrocyte sedimentation rates, white blood cell counts, and platelet counts were significantly elevated in patients who underwent amputation. Albumin levels were significantly suppressed in the amputation group. Univariate analysis showed that a 1-SD increase in baseline and post-treatment C-reactive protein levels, erythrocyte sedimentation rates, and white blood cell counts and a 1-SD decrease in post-treatment albumin levels were significantly associated with increased risk of amputation. Post-treatment C-reactive protein level was strongly associated with amputation risk. CONCLUSIONS circulating levels of acute phase reactants were associated with amputation risk in diabetic foot infections.

Prospective evaluation of tumor size and hormonal status in adrenal incidentalomas

Background: Because of the increased use of imaging interventions, more subjects have been diagnosed with adrenal incidentaloma in recent years. Aim: To evaluate the risk of mass enlargement, hormone hypersecretion and development of adrenal carcinomas during short-term followup. Subjects and methods: There were 317 subjects with incidentally discovered adrenal tumors in the registry. Forty subjects were excluded because of clinically overt hormone secretion at diagnosis and subjects with complete data were included in radiological (no.=150) and hormonal (no.=150) follow-up. Radiological evaluation was performed with computed tomography (CT) and/or magnetic resonance imaging (MRI). There were 143 subjects with adrenal adenomas and 7 subjects with other tumor types (cyst or myelolipoma). Median follow-up duration was 24 months. Results: Increase in tumor size was detected in 25 subjects (17.4%) with adenomas and 1 subject with adrenal myelolipoma (14.3%). Decrease in tumor size was found in 7 subjects (4.8%) with adrenal adenomas. One patient was diagnosed with adrenocortical carcinoma during follow-up. In subjects with non-functioning adrenal adenoma (NFA, no.=120) or subclinical Cushing syndrome (sCS) (no.=30), no subject developed clinically overt hormone hypersecretion, while 8 (6%) subjects in the NFA group developed sCS. Tumor diameter and follow-up duration were significantly higher in subjects who developed sCS. Conclusion: In conclusion, we demonstrated that, despite being infrequent, adrenal tumors may increase in size, develop overt or subclinical hormone secretion or feature malignant transformation. Therefore, radiological and hormonal follow-up should be recommended to the patients. More investigations are needed for the establishment of long-term follow-up protocols.