Grażyna Bednarek-Tupikowska

Effects of oestradiol and oestroprogestin on erythrocyte antioxidative enzyme system activity in postmenopausal women

Objective  Data concerning the relationship between sex steroid hormones and the cellular antioxidative enzyme system are controversial. We investigated the effects of oestradiol deficiency after menopause and the influence of transdermal oestradiol therapy (ET) and hormonal (oestradiol plus medroxyprogesterone) replacement therapy (HT) on erythrocyte superoxide dismutase (SOD), glutathione peroxidase (GSH‐Px) and catalase (CAT). GSH and selenium (Se) concentrations were also estimated. Serum lipid peroxide (LPO) levels were measured as an indicator of free‐radical production and lipid peroxidation.

Left Ventricular Function Impairment in Patients With Normal-Weight Obesity Contribution of Abdominal Fat Deposition, Profibrotic State, Reduced Insulin Sensitivity, and Proinflammatory Activation

Background— Obesity predisposes to left ventricular (LV) dysfunction and heart failure; however, the risk of these complications has not been assessed in patients with a normal body mass index (BMI) but increased body fat content (normal-weight obesity, NWO). We hypothesized that LV performance in NWO may be impaired and sought to investigate potential contributors to cardiac functional abnormalities. Methods and Results— One hundred sixty-eight subjects (age, 38±7 years) with BMI <25kg/m2 and no history of any disease affecting the myocardium were classified on the basis of body fat content into 2 groups: with NWO and without NWO. Echocardiographic indices of LV systolic and diastolic function, including myocardial velocities and deformation, serological fibrosis markers, indicators of proinflammatory activation, and metabolic control, were evaluated. Subjects with NWO demonstrated impaired LV systolic and diastolic function, increased fibrosis intensity (assessed by procollagen type I carboxy-terminal propeptide [PICP]), impaired insulin sensitivity, and increased proinflammatory activation as compared with individuals with normal body fat. The independent correlates of LV systolic and diastolic function variables were as follows: for strain, IL-18 (&bgr;=−0.17, P<0.006), C-reactive protein (&bgr;=−0.20, P<0.002) and abdominal fat deposit (&bgr;=−0.20, P<0.003); for tissue S velocity, PICP (&bgr;=−0.21, P<0.002) and abdominal fat deposit (&bgr;=−0.43, P<0.0001); for tissue E velocity, abdominal fat deposit (&bgr;=−0.30, P<0.0001), PICP (&bgr;=−0.31, P<0.0001) and homeostasis model assessment of insulin resistance index (HOMA IR; &bgr;=−0.20, P<0.002); and for E/e′-PICP, IL-18 (both &bgr;=0.18, P<0.01) and HOMA IR (&bgr;=0.16, P<0.04). Conclusions— In patients with NWO, subclinical disturbances of LV function are independently associated with the extent of abdominal fat deposit, profibrotic state (as reflected by circulating PICP), reduced insulin sensitivity, and proinflammatory activation.

Effects of estrogen and estrogen-progesteron on serum nitric oxide metabolite concentrations in post-menopausal women

UNLABELLED Estrogens have some anti-atherosclerotic properties and they influence nitric oxide (NO) production. The aim of this study was to determine NOx levels in post-menopausal women and the effect of estrogen/estrogen-progesteron therapy (ET/EPT) on plasma NO levels. Eighty postmenopausal women (M1) comprising 26 with surgically induced menopause (ET1), mean age 50.9+/-2.9 yr, and 54 with physiological menopause (EPT1), mean age 50.5+/-3.0 yr, were studied. Forty healthy pre-menopausal women, mean age 48.3+/-2.3 yr were the controls (C). The post-menopausal women were treated for 4 months: group ET1 with ET and group EPT1 with EPT. Serum estradiol (E2), FSH, NOx and lipid profile before and after therapy were measured. NOx levels were lower in group M1 than in group C (8.75+/-1.57 vs 10.27+/-2.62, p<0.01) and increased after hormonal therapy (10.65+/-2.38). NOx concentration showed significant positive correlation with E2 (r=0.25, p<0.05). Total cholesterol (240.9+/-43.2), LDL-cholesterol (155.2+/-33.6), triglycerides (124.8+/-54.1), and apolipoprotein B (1.52+/-0.33) were higher in group M1 than in group C (223.1+/-44.3, 133.0+/-38.2, 108.3+/-52.9, and 1.12+/-0.36, respectively), and after ET/EPT they decreased to the values observed in group C. There were no correlations between NO and lipids or apolipoproteins. CONCLUSIONS ET and EPT improve NOx synthesis and endothelial relaxation. Medroxyprogesterone acetate added to E2 does not significantly influence NOx levels.

The role of fat mass and obesity-associated gene (FTO) in obesity — an overview

Obesity is an epidemic of the 21st century. The magnitude of this problem stems from its increasing prevalence and numerous metabolic complications caused by excessive fat accumulation. The pathogenesis involves both environmental and genetic factors, and FTO (fat mass and obesity-associated gene) is one of the most significant among genes predisposing to obesity. The role of FTO polymorphism in the development of obesity has been confirmed in many studies, but the effect varies significantly in different ethnic groups. Moreover, the exact mechanisms of FTO influence are yet to be explained. The association between FTO and lifestyle factors such as diet and physical activity has been extensively studied in recent years. This paper presents current knowledge about the role of FTO gene in the development of obesity and type 2 diabetes in different ethnic groups and the association between FTO polymorphism and lifestyle modifications predisposing to adiposity.

Evaluation of Selected Atherosclerosis Risk Factors in Women with Subclinical Hypothyroidism Treated with L-Thyroxine

BACKGROUND Subclinical hypothyroidism (SCH) is a common endocrine disorder, probably increasing cardiovascular (CV) risk. However, the relation between SCH and atherosclerosis risk factors remains unclear. OBJECTIVES The aim of the study was to evaluate selected atherosclerosis risk factors in women with SCH in comparison to a group of healthy women and women with overt hypothyroidism, as well as to investigate the influence of L-thyroxine replacement on those risk factors. MATERIAL AND METHODS The study group consisted of 187 obese women aged between 50 and 70 years: 100 women with SCH, 45 women with overt hypothyroidism and 42 women with TSH level in reference ranges. Anthropometric parameters were evaluated. Laboratory tests included thyroid hormones concentrations, lipid profile with apolipoproteins, CRP, homocysteine. Atherosclerotic indexes were calculated: LDL C/HDL C ratio, apoA1/apoB ratio and Castelli risk index. Women with hypothyroidism were given L-thyroxine treatment and after 6 months in euthyroidism the evaluation was repeated. RESULTS Total cholesterol, LDL-cholesterol and triglycerides concentrations as well as LDL-C/HDL-C ratio and Castelli index were higher in SCH than in controls and decreased after L-thyroxin substitution. All of the calculated atherosclerosis indexes showed significant positive correlations with TSH concentration in SCH group. Also in this group the systolic and diastolic blood pressure decreased significantly after treatment. CONCLUSIONS Dyslipidemia in obese SCH women is not severe, but if untreated for many years, it may lead to atherosclerosis. Substitution therapy improves the lipid profile, changing the relations between protective and proatherogenic fractions of serum lipids, and optimises blood pressure.

Accumulation of abdominal fat in relation to selected proinflammatory cytokines concentrations in non-obese Wrocław inhabitants.

INTRODUCTION Metabolically obese normal weight (MONW) subjects, despite their normal BMI, present metabolic disturbances characteristic of abdominal obesity. One of the reasons might be subclinical inflammation caused by the fat tissue excess. The aim of this study was to assess the association between the accumulation of fat (especially abdominal) and the concentration of selected proinflammatory cytokines - interleukins (IL-6, IL-18) and C-reactive protein (CRP). MATERIAL AND METHODS The study population consisted of 342 subjects (218 women, 124 men; age 20-40 years, BMI < 27 kg/m2) recruited from a community centre in Wroclaw. The group was divided based on the homeostasis assessment insulin resistance index (HOMA) value: 90 MONW subjects with HOMA > 1.69 and 252 subjects as control group. Anthropometric parameters, serum IL-6, IL-18, CRP, glucose, insulin concentrations and insulin sensitivity/resistance indexes were evaluated. RESULTS CRP levels were significantly higher (3.26 vs. 1.97, p = 0.03) in MONW women than in the control group. Serum IL-6, IL-18 levels in males and females did not differ in both groups. IL-6 showed a significant correlation with the abdominal to gynoidal fat tissue deposit ratio in women. There were correlations between the CRP and BMI, WHR, waist circumference, total fat, abdominal fat deposit, and abdominal to gynoidal fat deposit ratio in both sexes. In women, positive correlations between CRP and HOMA, FIRI and negative with QUICKI index were present. CONCLUSIONS Increased accumulation of abdominal adipose tissue in non-obese, young and healthy subjects is related to increased CRP levels.

Current and emerging therapies for adrenocortical carcinoma--review.

Adrenocortical carcinoma (ACC) is a rare malignancy with poor prognosis. Patients may present with hormone excess or a local mass effect. The most common imaging techniques (CT and MRI) use both size and appearance to distinguish between benign and malignant tumors. Open surgery by an expert surgeon with R0 target is the treatment of choice. Mitotane (alone or in combination with cytotoxic drugs) may be administered after surgery or in patients not amenable to surgery. The role of radiotherapy as an adjuvant treatment is uncertain whereas targeted radionuclide therapy seems to be a promising option. New adjuvant treatment options, even after complete tumor removal, are desired because postoperative disease-free survival at 5 yrs is only around 30%. The establishment of detailed guidelines with the purpose of optimizing therapy with only mitotane but also in combination with other antineoplasmatic drugs is still a task to be done. Future advances in the management of ACC will probably be connected with better understanding of the molecular pathogenesis.

Are T2-weighted images more useful than T1-weighted contrast-enhanced images in assessment of postoperative sella and parasellar region?

Summary Background The proper diagnosis and management of patients after surgery for pituitary tumors are of great importance in clinical practice. The purpose of this study was to investigate the magnetic resonance features of the postoperative sella with fast spin echo T2-weighted imaging and to evaluate the benefits of this sequence compared to the classically performed contrast-enhanced T1-weighted imaging at 1.5T unit. Material/Methods The study group consisted of 101 patients who underwent resection of pituitary tumors. There were 58 women (57.4%), aged 22 to 75 (mean age, 52.67 years) and 43 men (42.6%), aged 21 to 79 (mean age, 49 years). In all patients preoperative and multiple postoperative MR studies were performed. Post-contrast T1 and pre-contrast T2 images were interpreted by 2 independent readers (neuroradiologists). Results Contrast-enhanced T1-weighted imaging was significantly superior to T2-weighted imaging in assessment of infundibulum (p<0.05). There was no statistically significant difference for each of readers between T1- and T2-weighted images regarding to the following features: visualization of residual pituitary gland (p=0.062 and p=0.368), contours of pituitary (p=0.959 and p=0.265), optic chiasm (p=0.294 and p=0.843), and visualization of presence of residual tumor (p=0.204 and p=0.169). T2-weighted images were significantly superior to contrast-enhanced T1-weighted imaging with regard to visualization of contours of residual tumors (p<0.05). Conclusions T2-weighted images may help to discriminate tumorous from non-tumorous involvement of the postoperative sella and the sphenoid sinus. T2-weighted images are also very useful for a long time after the resection in the postoperative evaluation of the implanted muscle with fascia.

Serum Lipid Transfer Proteins in Hypothyreotic Patients Are Inversely Correlated with Thyroid-Stimulating Hormone (TSH) Levels.

Background Plasma cholesteryl ester transfer protein (CETP) activity is often decreased in patients with hypothyroidism, whereas less is known about the phospholipid transfer protein (PLTP). We aimed to evaluate simultaneously serum CETP and PLTP activity in patients diagnosed with hypothyroidism. Material/Methods The selection criteria for control group members (without thyroid dysfunction) in this case to case study were levels of total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol (HDL-C), and triglycerides similar to those in study group patients (101 patients diagnosed with hypothyroidism). Serum CETP and PLTP activities were measured by homogenous fluorometric assays using synthetic donor particle substrates. Results Serum CETP and PLTP activities in hypothyreotic patients were lower (p<0.001) compared with those in healthy subjects. This lowering was associated with significant changes in HDL-C subclasses: decrease in HDL2- and increase in HDL3 cholesterol levels. Multiple linear regression analyses adjusted for age, sex, body mass index, smoking habits, and alcohol drinking showed a strong association between hypothyroidism and activity of lipid transfer proteins. A linear inverse relationship between thyroid-stimulating hormone (TSH) and CETP (r=−0.21; p<0.01) and between TSH and PLTP (r=−0.24; p<0.001) was shown. There also was a positive correlation (p<0.001) between CETP and HDL2 cholesterol (r=0.27) and between PLTP and HDL2 cholesterol (r=0.37). A negative correlation between CETP and HDL3 cholesterol (r=−0.22: p<0.01) and between PLTP and HDL3 cholesterol (r=−0.24; p<0.001) has been demonstrated as well. Conclusions The decreased HDL2 and increased HDL3 cholesterol levels in subjects with hypothyroidism are consequences of decreased activity of lipid transfer proteins. These changes are early symptoms of lipid disturbances in hypothyroidism.

VDR gene polymorphisms in Alzheimer's disease: pilot study

Introduction Aggravation of the symptoms of Alzheimers disease may also underlie the functioning of receptors associated with calcium and vitamin D. Therefore, it seems reasonable to study the correlation of polymorphisms of vitamin D receptor (VDR) and calcium receptor (CASR) with symptoms of AD. Alzheimers disease, vitamin D deficiency and osteoporosis often coexist in the patient. Research suggests that vitamin D deficiency is much more frequent in the patients with AD. Expression of VDR gene occurs in a neuronal and a glial cells. VDR belongs to the nuclear receptor superfamily and acts as a ligand activated transcription factor.