Baris Onder Pamuk

Serum total antioxidant status and lipid peroxidation marker malondialdehyde levels in overt and subclinical hypothyroidism

Background  Mitochondria are the main production site of free oxygen radicals, which can cause organ dysfunction by oxidation of cellular macromolecules such as carbohydrates, lipids and proteins. Oxidative stress may result from either overproduction of these species or from failure of the antioxidant defence systems. Thyroid hormones have well‐known effects on mitochondrial oxygen consumption, but data about how hypothyroidism affects oxidative stress are controversial, and little is known about oxidative stress in subclinical hypothyroidism. Total antioxidant status (TAS) gives information about all of the antioxidants in the organism, while malondialdehyde (MDA) is a lipid peroxidation marker used to assess lipid peroxidation due to increased oxidative stress. We aimed to determine how hypothyroidism and subclinical hypothyroidism affect serum MDA and TAS.

Impaired coronary microvascular function and increased intima-media thickness in rheumatoid arthritis

BACKGROUND Rheumatoid arthritis (RA) is associated with excessive cardiovascular mortality. Recently, some studies have shown endothelial dysfunction in RA patients with high inflammatory activity. In addition, it has been suggested that the chronic inflammatory state of RA contributes to accelerated atherosclerosis. Therefore, we aimed to evaluate whether coronary microvascular dysfunction and increased carotid artery intima-media thickness exist in patients with a long history and well controlled disease activity of RA lacking traditional cardiovascular risk factors. METHODS Thirty RA patients (22 women; mean age 43.7+/-9.0) and 52 healthy volunteers (38 women; mean age 45.3+/-5.4) were included into the study. Using transthoracic echocardiography, each subject underwent echocardiographic examination including coronary flow reserve (CFR) and carotid intima-media thickness (IMT) measurement. RESULTS CFR values were statistically reduced for RA patients as compared to controls (2.4+/-0.5 vs. 2.7+/-0.4, P=0.002) whereas IMT values were significantly increased (0.6+/-0.1 vs. 0.5+/-0.1, P=0.001). In RA patients, CFR positively correlated with lateral Em/Am ratio (r=0.399, P=0.029), and negatively correlated with lateral isovolumic relaxation time (IVRT) (r=-0.744, P=0.005), IMT (r=-0.542, P=0.002) and RA disease duration (r=-0.495, P=0.005). Reflecting LV diastolic function, mitral E-wave deceleration time and isovolumic relaxation time were borderline significant between the groups, however lateral Em/Am ratio and lateral IVRT were statistically different. CONCLUSIONS Patients with RA had impaired CFR and increased carotid IMT, and these injurious effects correlated significantly with disease duration.

Polycystic ovary syndrome is associated with elevated plasma soluble CD40 ligand, a marker of coronary artery disease

OBJECTIVE To determine the level of plasma soluble CD40 ligand (sCD40L) in patients with polycystic ovary syndrome (PCOS). DESIGN Prospective study. SETTING Baskent University School of Medicine in Turkey. PATIENT(S) Thirty-one patients with PCOS and 31 non-PCOS (control) patients. INTERVENTION(S) Determination of plasma sCD40L and homocysteine levels. MAIN OUTCOME MEASURE(S) Plasma sCD40L, fasting glucose, fasting insulin, homeostatic model assessment insulin resistance index (HOMA-IR), LH, FSH, E(2), total T, DHEAS, total cholesterol, high- and low-density lipoprotein cholesterol, triglyceride, homocysteine, and high-sensitivity C-reactive protein (hsCRP). RESULT(S) The mean serum fasting insulin and HOMA-IR levels were significantly higher in the PCOS group. The mean serum homocysteine level was significantly higher in the PCOS group. Despite a trend for higher high-sensitivity C-reactive protein levels in the PCOS group, the difference did not reach statistical significance. The mean plasma sCD40L level in the PCOS group was significantly higher than that in the control group (5.14 +/- 3.65 ng/mL vs. 3.45 +/- 2.64 ng/mL, respectively). CONCLUSION(S) Polycystic ovary syndrome is associated with elevated levels of sCD40L and homocysteine.

Evaluation of brain natriuretic peptide levels in hyperthyroidism and hypothyroidism.

BACKGROUND Brain natriuretic peptide (BNP) is secreted from the ventricular myocardium in response to volume expansion and pressure overload. Serum BNP levels are also affected by thyroid function status, which was mostly related to a direct stimulatory effect of thyroid hormones on the secretion of BNP. Although the diagnostic value of BNP in heart failure is undisputed, its value in the presence of the thyroid dysfunction has been recently questioned. The aim of this study was to evaluate the influence of thyroid dysfunction on BNP levels. METHODS Evaluation of 18 overt and 47 subclinical hyperthyroid patients together with 39 subclinical and 13 overt hypothyroid patients was carried out in a cross-sectional study. Thirty-three age-, sex- and body mass index (BMI)-matched control subjects were also included. RESULTS BNP levels were more than five times higher in hyperthyroid than euthyroid control subjects (P < 0.001). BNP levels were also higher in subclinical hyperthyroidism than euthyroid control subjects (P = 0.09). Correlation analysis revealed that free T4 and free T3 concentrations were associated with high serum BNP levels. The BNP level in patients with subclinical or overt hypothyroidism was similar to that of the controls. CONCLUSION The current study provides additional insight into the diagnostic value of BNP in the presence of coexistent thyroid dysfunction and demonstrates important independent effects of thyroid hormones upon BNP plasma concentrations.

49,XXXXY syndrome with autoimmune diabetes and ocular manifestations.

Objective: We report a rare case of 49,XXXXY syndrome with autoimmune diabetes (requiring insulin therapy), bilateral cataracts and unilateral glaucoma. Clinical Presentation and Intervention: A 25-year-old man with mental retardation presented with multiple skeletal abnormalities, polyuria and polydipsia. He had high glucose concentrations, without ketonuria, and hypergonadotropic hypogonadism. Ophthalmic examination revealed a polar cataract in both eyes and increased intraocular pressure in the left eye. The anti-islet cell antibody test was positive, and anti-glutamic acid decarboxylase autoantibody levels were elevated. Karyotype analysis revealed 49,XXXXY. Intensive insulin therapy and testosterone replacements were started. Conclusion: The autoimmune nature of diabetes that we observed in our patient seems to be predisposed by hypogonadism. Cataract and glaucoma in this case seem to be the result of diabetes, and an association of these ocular manifestations with the syndrome 49,XXXXY seems unlikely.

Mean platelet volume in patients with polycystic ovary disease

Polycystic ovary syndrome (PCOS) is a frequently encountered clinical condition characterized by chronic anovulation and hyperandrogenism. There are many reports pointing to the causal links between PCOS and cardiovascular disease (CVD). Although the level of risk for CVD remains uncertain in PCOS, there is substantial evidence that insulin resistance, obesity, dyslipidemia, hypertension, hypercoagulable state, and markers of abnormal vascular function possibly contribute to increased CVD risk [1, 2]. Platelets play a crucial role in the pathogenesis of thrombotic diseases. Circulating platelets are heterogeneous in size, density, and reactivity. The mean platelet volume (MPV), the accurate measure of platelet size, is considered a marker and determinant of platelet function since larger platelets are hemostatically more reactive than platelets of normal size, increasing the propensity to thrombosis [3]. Elevated MPV levels have been shown to be an independent risk factor for CVD [4, 5]. We investigated MPV in patients with PCOS alongside a comparable group of healthy control subjects. Eighty-five newly diagnosed PCOS patients who have no propensity to thrombotic or bleeding disorder and 81 ageand BMI (body mass index)matched regularly menstruating healthy non-hirsute women as the controls participated in this study. Demographic details of subjects are presented in Table I. All MPV measurements were performed on automated blood counter Cell-Dyn 4000 (Abbott Diagnostics, Santa Clara, CA, USA). The other parameters measured in fasting blood sample were glucose, insulin, total cholesterol, high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), triglyceride, free testosterone and total testosterone, and estrogen. Glucose values obtained at 0, 30, 60, 90, and 120 minutes after a 75 g oral glucose tolerance test was also measured. Each subject’s level of insulin resistance was estimated based on the homeostasis model assessment insulin resistance (HOMA-IR) index. Clinical and laboratory features of patients with PCOS and control subjects are depicted in Table I. The MPV was significantly higher in patients with PCOS (8.5 1.4 fl) than control subjects (7.8 0.9 fl) (p1⁄4 0.002). There was no statistically significant difference regarding platelet absolute count in patients with PCOS (264 51 10/L) and control subjects (257 48 10/L). HOMA-IR index was significantly higher in patients with PCOS than control subjects (3.0 3.1 vs. 2.0 0.8, p1⁄4 0.02). We did not observe any significant correlation between MPV and age, BMI, HOMAIR, lipid parameters, and levels of estrogen, free and total testosterone in patients with PCOS. There was also no correlation between MPV and glucose values obtained at 0, 30, 60, 90, and 120 minutes after a 75 g oral glucose tolerance test. Although direct evidence for increased thrombotic risk is still lacking in patients with PCOS, increased propensity to thrombosis is suggested

Fetuin-A levels in hyperthyroidism

OBJECTIVE: Fetuin-A is a protein secreted from the liver that inhibits arterial calcification deposition and can contribute to insulin resistance. Hyperthyroidism is also associated with insulin resistance. It is not known whether hyperthyroidism has an effect on fetuin-A levels. METHODS: We measured fetuin-A levels and homeostasis model of assessment-insulin resistance before hyperthyroidism treatment was initiated and after euthyroidism was achieved. A total of 42 patients diagnosed with hyperthyroidism were enrolled in this study. Fetuin-A, insulin, high-sensitivity C-reactive protein, fasting blood glucose, free T3 (fT3), free T4 (fT4), and thyrotropin were measured before and after euthyroidism was established. RESULTS: Basal fasting blood glucose, high-sensitivity C-reactive protein, insulin, c-peptide, homeostasis model of assessment-insulin resistance, fT3, fT4 and fetuin-A levels were significantly decreased after euthyroidism was achieved (Table 1. Basal fasting blood glucose (r:0.407, p:0.008), high-sensitivity C-reactive protein (r:0.523, p<0.0001), insulin (r:0.479, p:0.001), homeostasis model of assessment-insulin resistance (r:0.541, p<0.0001), fT3 (r:0.492, p:0.001) and fT4 (r:0.473, p:0.002) were positively correlated with basal fetuin-A levels. Basal thyrotropin levels were significantly negatively correlated (r:-0.553, p<0.0001) with basal fetuin-A levels. CONCLUSION: Our findings suggest that hyperthyroidism influences fetuin-A levels.

Effects of raloxifene on platelet functions in patients with postmenopausal osteoporosis

Many studies have addressed the effects of estrogenic compounds on platelet function. Raloxifene is a selective estrogen receptor modulator (SERM), which is currently used for the treatment of postmenopausal osteoporosis. At present, there are no clinical data about the effects of raloxifene on platelet function. The purpose of this study was to determine if raloxifene at therapeutic doses affects platelet function in patients with postmenopausal osteoporosis. The effects of raloxifene on platelet function were investigated using a commercial platelet function analyzer (PFA-100) with collagen epinephrine and collagen adenosine 5′-diphosphate (ADP) cartridges. We studied platelet function of 30 patients with postmenopausal osteoporosis before and 15 days after initiation of raloxifene 60 mg/daily. Closure times did not differ significantly between samples obtained before (117.8 ± 20.5 s) and after raloxifene therapy (106.5 ± 25.4 s) in collagen/epinephrine cartridges (P > 0.05). There was also no statistically significant difference in mean closure times with collagen/ADP cartridges at baseline (86.2 ± 18.5 s) and after raloxifene therapy (84.4 ± 13.8 s) (P > 0.05). Platelet counts (278.3 ± 72.9 vs. 262.4 ± 56.7 109/L, P > 0.05) and mean platelet volumes (8.9 ± 1 vs. 9.1 ± 1 fL, P > 0.05) were not different before and after raloxifene therapy. Although estrogen related compounds do affect platelet function, there is suggestive data in our study that raloxifene in therapeutic dose exhibit no effect on platelet function in patients with postmenopausal osteoporosis.

Effect of family history of type-2 diabetes on coronary flow reserve and it's relationship with insulin resistance: an observational study.

OBJECTIVE Coronary microvascular function among offspring of patients with diabetes mellitus might be compromised when compared to persons with no first-degree relative with diabetes mellitus. The aim of the study was to evaluate effect of family history of type-2 diabetes on coronary flow reserve. METHODS In this observational study, we evaluated coronary flow reserve (CFR) via echocardiography of 95 subjects having a biological parent with type-2 diabetes and 34 healthy volunteers without any biological parent with type-2 diabetes. We have analyzed possible association with CFR and homeostasis model assessment - insulin resistance (HOMA-IR). Comparison analyses were made using independent samples t test, Chi-square test and one-way ANOVA. Association of independent variables with CFR was obtained by correlation analysis and stepwise linear regression model including potential confounders. RESULTS CFR was significantly lower in the positive family history group than in the controls. Moreover, when compared with controls, the subgroup of insulin-sensitive subjects in the positive family history group also had significantly reduced CFR (2.67±0.28 vs. 2.83±0.19; p=0.01). Correlation analysis revealed that CFR was inversely correlated with HOMA-IR, (r=-0.433), fasting glucose (r=-0.331), fasting insulin (r=-0.396), and hemoglobin (Hb)A1c (r=-0.405). When the positive family history group was divided into tertiles of insulin resistance (HOMA-IR <1.3, 1.3-2.6, and >2.6; Groups 1-2, and 3), there was a significant difference in CFR between Groups 1 and 2 and between Groups 1 and 3 (p<0.05 for all). Though statistically not significant, there was also a difference in CFR between Groups 2 and 3. In a linear regression model, only fasting glucose level was independent predictor of CFR (β=-677; p value =0.001, 95% CI: -0.061 and -0.019). CONCLUSION Nondiabetic first-degree relatives of patients with type-2 diabetes are at increased risk of developing coronary microvascular dysfunction.

Polycystic Ovary Syndrome and Cardiovascular Disease

Young women have an inferior risk of cardiac events, but this benefit fades after menopause, leaving them at risk to develop a cardiovascular disease (CVD) (StrambaBadiale, Fox et al. 2006). Endocrine and gynecologic diseases may have impact on this pattern. Ever since the classical notice of Stein and Leventhal in 1935 (Stein and Leventhal. 1935), interest in polycystic ovaries (PCO) and its accompanying syndrome (PCOS) has grown from a ‘‘gynecological curiosity to a multisystem endocrinopathy’’ (Homburg 1996). Actually, polycystic ovary syndrome (PCOS), is the most common female endocrinopathy in up to 10% in reproductive age and appears to be related with an increased cardiovascular risk (Talbott, Guzick et al. 1995; Cibula, Cifkova et al. 2000). The syndrome is characterized by chronic anovulation and hyperandrogenism (Franks 1995; Scarpitta and Sinagra 2000). Cardiovascular disease and type 2 diabetes are two potential major long-term sequelae of this condition that is worth of examination.