Zeynep Cantürk

Hemostatic System as a Risk Factor for Cardiovascular Disease in Women with Subclinical Hypothyroidism

Hypothyroidism has been associated with atherosclerosis. The mechanisms of atherosclerosis in patients with thyroid failure remain controversial. Hypofibrinolysis might be a risk factor for thromboembolic disease in subclinical hypothyroidism (SH). We measured fibrinolytic activity in patients with SH before and after levothyroxine (LT(4)) treatment and compared it to those of controls. We prospectively included 35 patients with SH and 30 healthy controls. We treated patients with LT(4) until almost 6 months after the euthyroid state has been achieved. We measured fibrinogen, D-dimer, antithrombin III (ATIII), plasminogen activator inhibitor-1 (PAI-1), tissue plasminogen activator (tPA) activity, and factor VII. Clinical and anthropometric variables were recorded for both groups. We found increased levels of fibrinogen, PAI-1, and factor VII and decreased levels of ATIII activity in patients compared to control (p < 0.001 and p < 0.05). Decrease of tPA was not significant (p > 0.05). At the end of the LT(4) treatment, significant decreases were determined in PAI-1 and factor VII (p < 0.05). In conclusion, our data suggest an important role of hypofibrinolytic and hypercoagulable state on the development of atherosclerosis in patients with SH and beneficial effects of LT(4 )treatment for decreasing the risk of atherosclerosis.

Serum levels of hepatoprotective peptide adiponectin in non-alcoholic fatty liver disease.

Objective Adiponectin is an adipose tissue-specific protein that has anti-inflammatory, antidiabetic and antiobesity effects. It has been suggested that adiponectin has a hepatoprotective role. Non-alcoholic fatty liver disease (NAFLD) is becoming more prevalent with increasingly adverse clinical outcomes. In this study, serum adiponectin levels were investigated in patients with NAFLD to determine its possible role on hepatic inflammation and injury. Methods Twenty-nine biopsy-proven NAFLD patients (14 women, 15 men) with elevated liver enzymes, 20 clinically diagnosed NAFLD patients (13 women, seven men) with normal liver enzymes, and 20 healthy adults (10 women, 10 men) were enrolled. From fasting blood samples, serum adiponectin levels were measured by enzyme-linked immunosorbent assay. The body mass index, serum glucose, insulin, cholesterol and triglyceride levels were determined. Results Serum adiponectin levels were 4.99±2.1, 9.49±3.91 and 7.74±4.41 μ/ml in the NAFLD with elevated liver enzymes, NAFLD with normal liver enzymes and healthy adult control groups, respectively. The mean serum adiponectin level in the NAFLD with elevated liver enzymes group was significantly lower than those of other groups tested (P<0.001). Insulin, cholesterol and triglyceride levels of NAFLD patients with elevated liver enzymes were significantly higher than control groups (P<0.05) but were not significantly different from the NAFLD group with normal liver enzymes (P>0.05). On histopathologic examination, the mean serum adiponectin levels of non-alcoholic steatohepatitis patients with grade 2 or more inflammatory activity was significantly lower than patients with grade 1 inflammatory activity (P=0.013). Conclusion Serum adiponectin levels are significantly lower in NAFLD patients with elevated liver enzymes. Non-alcoholic steatohepatitis patients show lower levels of adiponectin with higher grades of inflammation.

Association between Circulating Tumor Necrosis Factor-Alpha, Interleukin-6, and Insulin Resistance in Normal-Weight Women with Polycystic Ovary Syndrome

BACKGROUND Insulin resistance is a common finding in both obese and lean women with polycystic ovary syndrome (PCOS). Factors contributing to insulin resistance are still controversial. The purpose of the study was to compare the tumor necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6) concentrations in normal weight women with PCOS and a weightmatched healthy control group, and also to evaluate the role of these cytokines in the pathogenesis of insulin resistance. METHODS Thirty-two women with PCOS and 25 age- and weight-matched healthy controls participated in this study. Patients were evaluated clinically and by pelvic ultrasound. Fasting insulin, glucose, lipid profile, follicle-stimulating hormone (FSH), leutinizing hormone (LH), prolactin, testosterone, sex hormone binding globulin (SHBG), 17-hydroxyprogesterone, IL-6, TNF-alpha concentrations, and insulin sensitiviy indices homeostasis model assessment (HOMA) and quantitative insulin sensitivity check index (QUICKI) were measured. RESULTS TNF-alpha and IL-6 concentrations were significantly higher in women with PCOS than in the control group. Significant correlations were found between TNF-alpha serum concentrations and Body Mass Index (BMI), waist circumference, triglyceride concentrations, fasting insulin, and insulin resisitance indices (p < 0.001). IL-6 concentrations were correlated with fasting glucose and insulin resistance (p < 0.05). CONCLUSIONS The study demonstrated that TNF-alpha and IL-6 concentrations were elevated in normal weight women with PCOS. The findings may contribute to evidence of insulin resistance in lean women with PCOS.

Homocysteine Concentrations in Subclinical Hypothyroidism

Hyperhomocysteinemia is considered to be an independent risk factor for atherosclerotic heart disease, including coronary artery disease (CAD). It is already known that overt hypothyroidism gives rise to a slight hyperhomocysteinemia. However, the effects of subclinical hypothyroidism on the levels of homocysteine are not known. In this study, we have evaluated homocysteine levels and the effect of L‐thyroxine treatment in patients with subclinical hypothyroidism. For the purpose of the study we selected 33 women patients with the diagnosis of subclinical hypothyroidism but without clinical CAD. After a euthyroidism development period of almost four months, a further study was done on patients who had been treated with thyroid hormone. The patient group was compared with 25 healthy control female subjects who were of similar age. In the patient group, homocysteine levels prior to treatment were significantly higher than in the control group (P < 0.001). After L‐thyroxine treatment, homocysteine levels were reduced significantly. In summary, we found that homocysteine levels were in the normal range in subclinical hypothyroidism. However, when compared with the healthy control group, the difference between them was significant. On the other hand, therapy to produce euthyroidism caused a significant reduction in homocysteine levels.

Serum Ferritin Levels in Poorly‐ and Well‐Controlled Diabetes Mellitus

Serum ferritin level is related to body iron stores and is influenced by several diseases. We aimed to evaluate the association between serum ferritin concentration and the complications and nature of diabetes mellitus (DM). We examined association of ferritin concentration, fasting and post‐prandial glucose levels and glycated hemoglobin in 329 patients with type 2 diabetes mellitus and 269 healthy controls. In the present study, 41 of 150 poorly controlled diabetic patients and 31 of 119 cases had hyperferritinemia. We confirmed that serum ferritin was increased in diabetic patients as long as glycemic control is not achieved. There was also a correlation between ferritin level and diabetic retinopathy. In conclusion, this study showed an independent positive association between serum ferritin concentration and markers of glucose homeostasis.

EFFECTS OF GRANULOCYTE-MACROPHAGE COLONY -STIMULATING FACTOR ON INCISIONAL WOUND HEALING IN AN EXPERIMENTAL DIABETIC RAT MODEL

The exact nature of poor wound healing in diabetes is uncertain. Neutrophils play a critical role in the host defense mechanism, and it is suggested that impaired neutrophil functions cause healing difficulties with or without infections in diabetic patients. Granulocyte-macrophage colony-stimulating factor (GM-CSF) is used clinically when given systematically to increase the circulating neutrophils, but its wound-healing effects have not been systematically studied. This study was undertaken to examine the effects of GM-CSF on incisional wound healing in an experimental diabetic rat model. Forty rats were randomly divided into three groups, group I receiving saline as control, diabetes-induced group II receiving saline and diabetes-induced group III receiving GM-CSF. The anesthetized rats in all groups were wounded 21 days after diabetes induction by streptozotocin. Blood neutrophil counts and neutrophil fractions were also determined three days after wounding. Tensile strengths of wounded skin and the hydroxyproline (hyp) level of the wound were determined and wound healing processes were evaluated by light and electron microscopy, fourteen days after wounding. Neutrophil counts and phagocytosis were significantly increased in group III and neutrophil counts decreased in group II (p < 0.05). Although the hydroxyproline level of wound tissue significantly decreased in group II as compared with group III (p < 0.05), there was no differences of tensile strength between group II and III (p < 0.05). Wound score in group II was less than that in groups I and III (p < 0.05). It is concluded that PMN may have a role in modulating wound healing. GM-CSF may be useful for creating better wound healing healing. GM-CSF may be useful for creating better wound healing in risky patients such as diabetics.

Lipid Profile and Lipoprotein (a) as a Risk Factor for Cardiovascular Disease in Women with Subclinical Hypothyroidism

This study evaluated changes of lipids and lipoprotein (a) [Lp (a)] as atherosclerotic risk factors and the effects of levothyroxine (LT4) treatment on these parameters in patient with subclinical hypothyroidism (SH), defined by increased concentrations of thyrotropin (TSH) and normal thyroid hormone concentrations. We prospectively included 35 female patients with SH and 30 healthy controls. Serum lipid measurements and clinical score as well as fT3, fT4, and TSH levels were assessed at baseline. Body mass index (BMI) was also calculated. Women with proven SH received LT4 treatment that continued for 6 months. Twenty‐six of 35 patients completed the study. At the end of treatment period, the same parameters were determined. Total cholesterol was significantly increased in patients with SH when compared with those of controls (p < 0.01), but increase of LDL‐cholesterol (LDL‐C) and Lp (a) were not significant (p > 0.05). In the levothyroxine‐treated group, total cholesterol and LDL‐C were significantly reduced when compared with the baseline values of women with SH (p < 0.05). Zulewski clinical score assessing symptoms and signs of hypothyroidism improved significantly with treatment (p < 0.001). In conclusion, serum lipids as important atherosclerotic risk factors increased before treatment and decreased with treatment. Levothyroxine therapy is effective in SH and improvements in serum lipids suggests that LT4 treatment also decreases the risk of atherosclerotic diseases.

The Relationship between Neutrophils and Incisional Wound Healing

The systemic administration of granulocyte-macrophage colony-stimulating factor (GM-CSF) is used clinically to increase circulating neutrophils, but its wound healing effects after intraperitoneal treatment have not been studied yet. We planned to investigate the effect of neutrophils on wound healing under cyclophosphamide and GM-CSF treatment. Forty rats were divided into three groups: control group (group I, n = 12) receiving saline, group II (n = 14) receiving cyclophosphamide and group III (n = 14) receiving GM- CSF. The rats in all groups underwent incisional wounding and were euthanized after 7 days. Blood neutrophil counts and functions, tensile strengths and the hydroxyproline level of skin were determined, and a histopathological evaluation of healing was made. Neutrophil counts and phagocytosis significantly increased in group III and decreased in group II. Although the skin hydroxyproline level did not differ, there was a difference in tensile strength of the wounded skin between group II and group III. The wound score in group II was lower than that in groups III and I. As a result we suggest that systemically given GM-CSF – by increasing the neutrophil count and neutrophil phagocytosis index – can enhance the tensile strength of surgical incisions.

PREVALENCE AND COMPARISONS OF FIVE DIFFERENT DIAGNOSTIC METHODS FOR HELICOBACTER PYLORI IN DIABETIC PATIENTS

Helicobacter pylori is now regarded as a major gastroduodenal pathogen that is etiologically linked with duodenal and gastric disease. It has been suggested recently as an important factor for nongastroenterologic conditions such as coronary heart disease and diabetes mellitus. In this study, we planned to investigate the prevalence of H. pylori in diabetic patients and to evaluate five different diagnostic tests. Group I consisted of 67 patients with type II diabetes mellitus and seventy-three aged-matched health people served as control in group II. Group I was divided in two subgroups with good (Group IA) and poor (Group IB) glycemic control. H. pylori was diagnosed by five different tests: 1) biopsy, 2) culture, 3) gram staining, 4) imprint cytology and 5) brushing cytology. The usefulness of each test for each group was statistically compared. There was a higher prevalence for H. pylori in diabetic patients. This study showed that two positive out of five tests was most reliable for predicting the H. pylori in diabetic and nondiabetic patients. In conclusion, the prevalence of H. pylori is high in diabetic patients. Peristaltic activity, and impaired nonspecific immunity must be evaluated as risk factors in diabetics. We recommend that the ‘gold standard’ should be regarded as two positive out of these five different tests.

The effect of metformin on mean platelet volume in dıabetıc patients

Diabetes mellitus (DM) is an independent risk factor for cardiovascular diseases. Metformin, the most commonly used antidiabetic, also has an antiatherogenic effect. Mean platelet volume (MPV) is increased in patients with high thrombogenic activation and also at risk for atherosclerosis. The purpose of this study was to examine the effects of metformin on MPV values in newly diagnosed type II DM patients on metformin monotherapy. In this study, 60 newly diagnosed type II DM patients (45 females, 15 males), who had applied to the Kocaeli University School of Medicine Endocrinology outpatient clinic, and 47 healthy individuals (35 females, 12 males) were included. The two groups have similarity for age, sex and body mass index. The patients with additional disease, nephropathy, smoking and using drugs that may affect the MPV were excluded. At baseline and 6 months after metformin treatment, patient demographics and laboratory values were compared. MPV was higher among type II DM patients than the control group (p < 0.001). After 6 months of metformin treatment, MPV values were significantly decreased (p < 0.001). HbA1c and mean platelet mass were also significantly decreased (p = 0.022 and 0.001, respectively). There was no correlation between MPV and HbA1c values (r = −0.13, p = 0.926). Metformin, which has been shown to exhibit antiatherogenic effect through positive effects on cholesterol levels, inflammatory markers and vascular adhesion molecules, decreased MPV values that appear to play a crucial role at the beginning of atherosclerosis development. We conclude that our result may contribute to the explanation for antiatherogenic effect of metformin.