Dilek Gogas Yavuz

Effects of ACE inhibition and AT1-receptor antagonism on endothelial function and insulin sensitivity in essential hypertensive patients

Objective Disturbed endothelial function is closely associated with hyperinsulinaemia and insulin resistance in essential hypertension. The aims of this study were: 1) to evaluate whether the two alternative drugs, angiotensin-converting enzyme (ACE) inhibitors and Angiotensin II (Ang II) antagonists, had comparable effects on glucose metabolism and endothelial function. 2) to determine whether they improve endothelial dysfunction through modulating insulin resistance and oxidative stress. Study design and methods Study design and methods Essential hypertensive patients were randomised into two groups: Twelve (nine patients in final analysis) patients were given enalapril (enalapril group), and twelve (nine patients in final analysis) were given losartan (losartan group). Twelve sex- and age-matched normotensive volunteers were included as controls. Before and after six months of treatment, endothelial function, insulin sensitivity and lipid peroxidation (TBARs) and NO metabolites (NOx) were evaluated. Results Endothelial function, measured as flow mediated dilatation (FMD), was improved in both of the treatment groups (p=0.0001). Calculated insulin sensitivity index also improved in the enalapril-treated group (p=0.05) but not in the losartan-treated group, compared with baseline levels. TBARS values decreased significantly in the enalapril group compared with baseline levels (p<0.001). FMD was positively correlated with insulin sensitivity index (r=0.32, p<0.05) and NOx levels (r=0.39, p=0.01) and negatively correlated with TBARS levels (r=-0.53, p=0.0002) in hypertensive patients. Conclusion Inhibition of the renin-angiotensin system, either with ACE inhibitors or AT1-receptor blockers improves endothelial dysfunction. ACE inhibition has prominent effects on improving insulin sensitivity and decreasing oxidative stress in essential hypertensive patients.

Epicardial Fat Tissue Thickness Correlates with Endothelial Dysfunction and Other Cardiovascular Risk Factors in Patients with Metabolic Syndrome

BACKGROUND Epicardial adipose tissue has shown to be related to cardiovascular risk. The aim of this study is to investigate the relationship between epicardial adiposity and endothelial function in metabolic syndrome. METHODS Fifty patients with metabolic syndrome were recruited. Anthropometric measurements, fasting blood glucose, insulin, lipid profile, high-sensitivity C-reactive protein (hsCRP), fibrinogen, apolipoprotein A (Apo A), Apo B1, and lipoprotein (a) [Lp(a)] were determined. Homeostasis model assessment of insulin resistance (HOMA-IR) was calculated. Epicardial fat thickness was measured via two-dimensional M-mode echocardiography. Endothelial function was assessed as flow-mediated dilatation at the brachial artery. RESULTS Epicardial fat tissue thickness was shown to be correlated negatively with FMD and positively with age, diastolic blood pressure, hsCRP, fibrinogen, HOMA-IR, and lipid parameters. Multiple regression analysis showed epicardial fat tissue thickness to be an independent factor influencing the endothelial function. CONCLUSIONS Epicardial fat tissue may be a useful parameter in the assessment of patients with metabolic syndrome.

Association of serum paraoxonase activity with insulin sensitivity and oxidative stress in hyperthyroid and TSH-suppressed nodular goitre patients

objective  Low serum paraoxonase (PON) activity is thought to be a risk factor for the development of atherosclerosis. The present study was designed to evaluate PON1 activity and its relationship with preatherosclerotic markers such as lipid peroxidation and insulin resistance in hyperthyroid patients before and after propylthiouracil (PTU) treatment and in subjects with iatrogenic subclinical hyperthyroidism.

Macroprolactin does not contribute to elevated levels of prolactin in patients on renal replacement therapy

Objective  Three molecular forms of PRL with molecular weights of 23, 50–60 and > 100 kDa have been defined. The high‐molecular‐weight forms are called macroprolactin. Different immunoassays produce varyingly elevated results with macroprolactin‐containing sera. The kidneys are reported to clear 25% of PRL from the circulation. Hyperprolactinaemia is seen in 20–75% of patients with chronic renal failure (CRF). PRL clearance rate has been reported to be reduced in CRF and the resulting hyperprolactinaemia is due to reduced renal function.

Effects of captopril and losartan on lipid peroxidation, protein oxidation and nitric oxide release in diabetic rat kidney

Increased oxidative stress has an important role in the pathogenesis of diabetic nephropathy. The aim of this study was to evaluate the effects of renin-anigiotensin system blockage, either by angiotensin-converting enzyme inhibition or angiotensin receptor blockage, on oxidative stress and nitric oxide release in diabetic rat kidneys. After induction of diabetes, six rats were given captopril, six rats were given losartan, and six rats served as diabetic controls. Six healthy rats were also included. At the end of an 8-week period nitric oxide release, lipid peroxidation and protein oxidation were measured in kidney cortices, and urinary albumin excretion (UAE) was determined in 24-h urine samples. Losartan- and captopril-treated diabetic rats had lower levels of UAE than diabetic controls. Diabetic rats had higher levels of lipid peroxidation and protein oxidation compared to healthy rats. NO release was significantly lower in diabetic groups than healthy controls. UAE levels showed a positive correlation with lipid peroxidation and a negative correlation with NO release. Inhibition of lipid peroxidation could be one of the protective mechanisms of renin-angiotensin axis inhibition in diabetic kidney tissues.

Circulating endothelial cells are elevated in patients with type 1 diabetes mellitus

OBJECTIVE Circulating endothelial cells (CECs) have emerged as vascular damage markers and are increased in type 2 diabetic patients. Since type 1 diabetes is associated with vascular damage, we hypothesized high CEC numbers in this patient population. METHODS Thirty-nine patients with type 1 diabetes and 39 controls were included. CECs were isolated using anti-CD146-coated Dynabeads, stained with Ulex lectin-1, and counted by fluorescence microscopy. Endothelial function was measured as flow-mediated dilation (FMD). Thiobarbituric acid reactive substances (TBARS), total glutathione levels (GSH), and paraoxonase (PON) activity levels were measured as oxidative stress markers. RESULTS Patients with type 1 diabetes mellitus had higher number of CECs (7.46+/-5.37 vs 2.13+/-1.13 cells/ml, P<0.001), lower FMD (7.87+/-2.19 vs 12.06+/-2.34%, P<0.001), higher TBARS (4.94+/-1.20 vs 3.07+/-0.75 nmol/MDA, P<0.001), lower GSH (206.12+/-98.06 vs 353.61+/-68.45 microM, P<0.001), and lower PON activity levels (89.10+/-17.82 vs 127.65+/-29.01 U/l, P<0.001) as compared to controls. There was positive correlation between CEC numbers and HbAlc levels (r=0.49, P=0.002). CECs and fasting glucose levels were not correlated. There was no correlation between the number of CECs and FMD. Furthermore, there were no correlations between the number of CECs and TBARS, GSH and PON activity levels. Multiple regression analysis showed that HbAlc levels (r(2)=0.40, P<0.009) were associated with CEC numbers. CONCLUSION CECs are elevated in patients with type 1 diabetes mellitus reflecting endothelial damage. This increase is dependent on long-term glucose control.

Effects of ACE inhibition and angiotensin II receptor blockade on glomerular basement membrane protein excretion and charge selectivity in type 2 diabetic patients.

Angiotensin-converting enzyme (ACE) inhibitors may reduce urinary albumin excretion (UAE) by decreasing glomerular pressure and increasing glomerular charge selectivity through preservation of glycosaminoglycans. The effect of Angiotensin II antagonism on glomerular charge selectivity remains to be determined. The aim of this study was to compare the effects of an AT1 blocker losartan and an ACE inhibitor (ACE-I) enalapril on UAE, extracellular matrix proteins, glycosaminoglycan excretion (UGAG) and red blood cell anionic charge (RBCCh) which are the indirect markers of glomerular basement membrane anionic content in hypertensive Type 2 diabetic patients. Twenty-four patients were randomised into two groups and received either enalapril (5—20 mg/d) or losartan (50—100 mg/d). All parameters were measured at baseline and after six months of treatment. At the end of six months, systolic and diastolic blood pressures (BP), UAE rates, UGAG excretion and RBCCh were significantly and equally reduced in both treatment groups compared with baseline. RBCCh was negatively correlated with UAE (r=-0. O 57, p<0.0001) and UGAG excretion (r=-0.57, Rp<0.0001); UAE was correlated with UGAG excretion (r=0.58, p<0.0001). In conclusion, enalapril and losartan treatment were equally effective in reducing BP, UAE as well as UGAG excretion and preserving RBCCh in hypertensive Type 2 diabetic patients. ACE inhibition and AT1-receptor blockade may have favourable effects on preserving glomerular anionic content in hypertensive diabetic patients.

V30 as a predictor for radiation-induced hypothyroidism: a dosimetric analysis in patients who received radiotherapy to the neck.

IntroductionThe purpose of this study is to evaluate the possible predictors of thyroid disorders after neck radiotherapy, with a focus on radiation dose-volume factors.MethodsThyroid function was measured in 100 patients who had received radiotherapy to the neck, including the thyroid. All radiation-induced thyroid dysfunctions were determined with an endpoint of abnormal thyroid stimulating hormone (TSH), free triiodothyronine (fT3) and thyroxine (fT4) and thyroid peroxidase antibodies and (TPA). The total volume of the thyroid, mean radiation dose to the thyroid (Dmean) and thyroid volume percentage that received radiation doses of 10–50 Gy (V10-V50) were calculated in all patients. The evaluated risk factors for thyroid dysfunction included dose-volume parameters, sex, age, previous surgery, chemotherapy and comorbidity.ResultsThere were 52 patients with hypothyroidism and V30 (p = 0.03), thyroid volume (p = 0.01) and Dmean (p = 0.03) appeared to be correlated with hypothyroidism in univariate analysis. However, there was not association found in multivariate analysis for these factors.ConclusionsThyroid disorders after radiation therapy to the neck still represent a clinically underestimated problem. V30 may be a useful tool for evaluating the risk of hypothyroidism when determining an individual patient’s treatment.

Vitamin D receptor gene polymorphisms in a group of postmenopausal Turkish women: association wıth bone mineral density.

Objective To determine the frequency of the vitamin D receptor (VDR) gene polymorphisms BsmI, ApaI, TaqI and FokI and their associations with bone mineral density (BMD) in postmenopausal Turkish women. Design One hundred and thirty healthy postmenopausal women and 130 premenopausal healthy women acting as controls were included in the study. The BsmI, FokI, ApaI and TaqI polymorphisms in the VDR gene were studied by polymerase chain reaction–restriction fragment length polymorphism method. The BMD of the lumbar vertebrae and femur neck were measured by dual-energy X-ray absorptiometry. Comparisons between the groups were performed using the paired t-test and ANOVA. χ2 or contingency tables were used to analyze qualitative results. Results Genotypes BB, Bb and bb occurred in premenopausal women with frequencies of 16.92%, 50% and 33.08% and in postmenopausal women with frequencies of 16.92%, 56.15% and 26.92%, respectively. Genotypes FF, Ff, ff occurred in premenopausal women with frequencies of 47.69%, 42.31% and 10% and in postmenopausal women with frequencies of 50.77%, 42.31% and 6.92%, respectively. Genotypes AA, Aa, aa occurred in premenopausal women with frequencies of 23.85%, 56.15% and 20% and in postmenopausal women with frequencies of 26.15%, 46.15% and 27.70%, respectively. Genotypes TT, Tt and tt occurred in premenopausal women with frequencies of 37.69%, 45.38% and 16.92% and in postmenopausal women with frequencies of 39.23%, 45% and 15.38%, respectively. There was no difference in the frequencies of VDR gene polymorphisms between premenopausal and postmenopausal women. BMD measurements were not different between genotypes in premenopausal and postmenopausal women. Conclusions The VDR gene BsmI, FokI, ApaI and TaqI polymorphisms have no major influence on bone mineral density in our group of postmenopausal women.

Exogenous subclinical hyperthyroidism impairs endothelial function in nodular goiter patients.

BACKGROUND Exogenous subclinical hyperthyroidism is associated with cardiovascular and metabolic changes. The aim of this study was to evaluate the effect of levothyroxine (LT4) suppression on endothelial function and insulin sensitivity in euthyroid nodular goiter patients. METHODS Twenty-two euthyroid patients with multinodular goiter (MNG) and 22 matched healthy controls were studied. LT4 was administered in doses ranging from 50 to 150 microg/day to reach target serum thyroid-stimulating hormone (TSH) levels <0.5 mIU/L. Patients were studied before and after 8 weeks after the target TSH level <0.5 mIU/L. The control group was studied twice, 16 weeks apart. Flow mediated vasodilatation (FMD), insulin sensitivity index (ISI), lipid peroxidation, and high-sensitivity C-reactive protein (hsCRP) were the outcome measures. RESULTS LT4 treatment significantly suppressed TSH levels to 0.2 +/- 0.1 mIU/L (minimum and maximum range was 0.05-0.3 mIU/L). FMD decreased from 10.7 +/- 2.7% to 5.4 +/- 1.7% (p < 0.001) and mean ISI decreased from 2.56 +/- 1.10 to 1.41 +/- 0.50 (p < 0.001) with LT4 treatment in the MNG group. Lipid peroxidation measured as thiobarbituric acid reactive substances (Tbars) (p < 0.05), and hsCRP (p < 0.001) levels significantly increased compared to the baseline in the MNG group. FMD measurement inversely correlated with free T4 (p = 0.008) and Tbars (p = 0.004), and positively correlated with ISI (p = 0.004). Serum Tbars and hsCRP were independent predictors of FMD (p = 0.004) in multivariate analysis. All results expressed as mean +/- SD. CONCLUSIONS TSH suppression therapy with LT4 leading to subclinical hyperthyroidism may cause impaired endothelial function, increased oxidative stress, and decreased insulin sensitivity in euthyroid nodular goiter patients.