Polimorfizm S-transferazy glutationowej (GST) może być wczesnym markerem w rozwoju zespołu policystycznych jajników (PCOS) — doświadczenia nieotyłych dorosłych pacjentów z cukrzycą insulinoniezależną

Introduction: It has been supposed that endocrine disturbances might be responsible for polycystic ovary syndrome (PCOS)-associated oxida­tive stress, with special emphasis on hyperandrogenism. Considering the potential relationship between hyperandrogenism and increased free radical production, parameters of oxidative stress were determined in non-obese normoinsulinemic adolescent girls newly diagnosed with PCOS. Materials and methods: Nitrotyrosine, thiol group concentrations, glutathione peroxidase, and superoxide dismutase activities were determined under fasting conditions and during oral glucose tolerance test (OGTT) in 35 PCOS patients and 17 controls. Insulin resistance was assessed by the homeostasis model (HOMA-IR), HOMA β, insulinogenic index (IGI), Matsuda insulin sensitivity index (ISI), and AUC for glucose. Glutathione S-transferases (GSTs) polymorphisms were determined by PCR. Results: Under fasting conditions, no significant difference of oxidative stress parameters was found between PCOS and controls. Acute hyperglycaemia during OGTT induced significant alteration in parameters of oxidative protein damage in PCOS patients. Alteration in nitrotyrosine concentrations correlated with testosterone, DHEAS, androstenediones, FAI, and LH, while changes in thiol groups cor­related with DHEAS. Significant inverse association was found between LH and ISI, as well as AUC glucose and thiol groups. PCOS girls, carriers of GSTM1-null genotype, had significantly lower testosterone in comparison to ones with GSTM1-active genotype. Conclusions: PCOS girls exhibited high free radical production together with unchanged antioxidant enzymatic capacity, independently from obesity and insulin resistance. Based on associations between oxidative stress parameters and testosterone, DHEAS, and androsten­edione, it can be suggested that increased free radical production, probably as a consequence of hyperandrogenaemia, is an early event in the development of PCOS

Evaluation of a Summary Score for Dyslipidemia, Oxidative Stress and Inflammation (The Doi Score) in Women with Polycystic Ovary Syndrome and its Relationship with Obesity

Background: Polycystic ovary syndrome (PCOS) is a cardiornetabolic disorder whose features include dyslipidemia, increased oxidative stress (OS, oxy) and chronic inflammation. The aim of this study was to investigate the ability of a summary score for dyslipidemia, OS and inflammation (the DOI score) to discriminate PCOS patients from healthy individuals and to evaluate the effect of obesity on individual scores and the DOI score in patients. Methods: Lipid status parameters, OS status parameters (advanced oxidation protein products; total oxidative status; prooxidant-antioxidant balance; malondialdehyde; total protein sulphydryl groups and paraoxonase 1 activity) and CRP were measured in 114 patients and 50 controls using standardised assays. The DOI score was calculated as the sum of dyslipidemia, oxy and inflammation scores, determined as Z-score values for every subject in relation to the controls. Results: PCOS patients had significantly higher oxy-score compared to controls (P lt 0.001). In addition, the DOI score was significantly higher in PCOS patients (P lt 0.001) as the dyslipidemia (P lt 0.05) and inflammatory scores (P lt 0.001) were greater. According to ROC analysis, the oxy-score showed better diagnostic accuracy in discriminating PCOS patients compared to the DOI score (AUC>0.9, P lt 0.01). Furthermore, obesity affected the risk scores in patients, especially the DOI score (significantly higher DOI scores in such patients, P lt 0.001). Conclusion: PCOS patients had greater dyslipidemia, chronic inflammation and OS compared to controls and could be segregated using all four scores. Our data suggest that weight gain could be the common factor responsible for induction and propagation of dyslipidemia, OS and inflammation in PCOS patients

Body mass index rather than the phenotype impacts precocious ultrasound cardiovascular risk markers in polycystic ovary syndrome

Objective Research into cardiovascular disease (CV) prevention has demonstrated a variety of ultrasound (US) markers predicting risk in the general population but which have been scarcely used for polycystic ovary syndrome (PCOS). Obesity is a major factor contributing to CV disease in the general population, and it is highly prevalent in PCOS. However, it is still unclear how much risk is attributable to hyperandrogenism. This study evaluates the most promising US CV risk markers in PCOS and compares them between different PCOS phenotypes and BMI values. Design Women fulfilling the Rotterdam criteria for PCOS were recruited from our outpatient clinic for this cross-sectional study. Methods Participants (n\u2009=\u2009102) aged 38.9 \ub1 7.4 years were stratified into the four PCOS phenotypes and the three BMI classes (normal-weight, overweight, obese). They were assessed for clinical and biochemical parameters together with the following US markers: coronary intima-media thickness (cIMT), flow-mediated vascular dilation (FMD), nitroglycerine-induced dilation (NTG), and epicardial fat thickness (EFT). Results There was no statistical difference among the four phenotypes in terms of cIMT, FMD, NTG or EFT, however all the US parameters except NTG showed significant differences among the three BMI classes. Adjusting for confounding factors in multiple regression analyses, EFT retained the greatest direct correlation with BMI and cIMT remained directly correlated but to a lesser degree. Conclusions This study showed that obesity rather than the hyperandrogenic phenotype negatively impacts precocious US CV risk markers in PCOS. In addition, EFT showed the strongest association with BMI, highlighting its potential for estimating CV risk in PCOS

Acetylcholinesterase as a potential target of acute neurotoxic effects of lindane in rats

Abstract. The aim of our study was to investigate the possible involvement of acetylcholinesterase (AchE) in mediating the early phase of acute lindane neurotoxicity in rats. Male Wistar rats (n = 48) were divided into following groups: 1. control, saline-treated group; 2. dimethylsulfoxidetreated group; 3. group that received lindane dissolved in dimethylsulfoxide, in a dose of 8 mg/kg intraperitoneally. Eight animals from each group were sacrificed 0.5 and 4 h after treatment and brain samples were prepared for further analysis. AchE activity (mitochondrial and synaptosomal fraction) was determined in cerebral cortex, thalamus, hippocampus and nc. caudatus spectrophotometrically. A significant increase in mitochondrial AchE activity was detected in cortex and nc. caudatus of lindane-treated animals 0.5 h after administration (p < 0.05). This rise was sustained in nc. caudatus within 4 h after treatment (p < 0.05). In contrast, activity of synaptosomal AchE fraction was significantly increased only in thalamus 4 h after lindane administration (p < 0.05). An increase in AchE activity may be involved in mediating acute neurotoxic effects of lindane, at least in some brain structures in rats

Premature Adrenarche and its Association with Cardiovascular Risk in Females

Early activation of the adrenal zona reticularis, leading to adrenal androgen secretion, mainly dehydroepiandrosterone sulfate (DHEAS), is called premature adrenarche (PA). The fact that adrenal hyperandrogenism in females has been linked to a cluster of cardiovascular (CV) risk factors, even in prepubertal children, warrants investigation. Controversial results have been obtained in this field, probably due to genetic, constitutional, and environmental factors or differences in the characteristics of participants. In an attempt to understand, in depth, the impact of PA as a potential activator of CV risk, we critically present available data stratified according to pubertal status. It seems that prepubertally, CV risk is increased in these girls, but is somewhat attenuated during their second decade of life. Furthermore, different entities associated with PA, such as polycystic ovary syndrome, non-classical congenital adrenal hyperplasia, heterozygosity of CYP21A2 mutations, and the impact of DHEAS on CV risk, are reviewed. At present, firm and definitive conclusions cannot be drawn. However, it may be speculated that girls with a history of PA display a hyperandrogenic hormonal milieu that may lead to increased CV risk. Accordingly, appropriate long-term follow-up and early intervention employing a patient-oriented approach are recommended

The role of transforming growth factor beta in thyroid autoimmunity: current knowledge and future perspectives

The complex mechanisms, which are related to the pathophysiology and the development of autoimmune thyroid diseases, involve transforming growth factor beta (TGF-beta) and its interplay with the immune system. The aim of this review is to examine the role of TGF-beta regarding thyroid autoimmunity and explore the potent role of this molecule either as a diagnostic or prognostic marker or a therapeutic target regarding autoimmune thyroid diseases. TGF-beta is clearly a master regulator of the immune response, exerting either inhibitory or facilitatory effects on cells of the immune system. Thus, this molecule is involved in the pathogenesis and development of autoimmune thyroid diseases. Recent research has revealed the involvement of TGF-beta in the pathophysiology of autoimmune thyroid diseases. The role of TGF-beta in the development of autoimmune thyroid diseases varies, depending on its concentrations, the type of the activated TGF-beta signalling pathway, the genetic predisposition of the patient and the pathophysiologic stage of the disease. TGF-beta could emerge as a useful diagnostic or prognostic marker for the evolution of thyroid autoimmunity. Promising perspectives for the effective therapeutic use of TGF-beta regarding thyroid autoimmunity exist. The main treatment approaches incorporate either enhancement of the immunosuppressive role of TGF-beta or inhibition of its facilitatory role in the autoimmune thyroid diseases. Further research towards deeper understanding of TGF-beta physiology and clinical application of its possible therapeutic role regarding thyroid autoimmunity is needed

Clinical relevance of 18F-FDG PET/CT in the postoperative follow-up of patients with history of medullary thyroid cancer

The aim of the study was evaluation of 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography with computed tomography (PET/CT) in the detection of active disease in the patients with suspected recurrence of the medullary thyroid carcinoma (MTC)