Multiple sclerosis (MS) is a chronic, inflammatory, neurodegenerative disease with an autoimmune component. It was suggested that potassium channels, which are involved in crucial biological ...functions may have a role in different diseases, including MS and its animal model, experimental autoimmune encephalomyelitis (EAE). It was shown that voltage-gated potassium channels Kv1.5 are responsible for fine-tuning in the immune physiology and influence proliferation and differentiation in microglia and astrocytes. Here, we explored the cellular distribution of the Kv1.5 channel, together with its transcript and protein expression in the male rat spinal cord during different stages of EAE. Our results reveal a decrease of Kv1.5 transcript and protein level at the peak of disease, where massive infiltration of myeloid cells occurs, together with reactive astrogliosis and demyelination. Also, we revealed that the presence of this channel is not found in infiltrating macrophages/microglia during EAE. It is interesting to note that Kv1.5 channel is expressed only in resting microglia in the naïve animals. Predominant expression of Kv1.5 channel was found in the astrocytes in all experimental groups, while some vimentin
+
cells, resembling macrophages, are devoid of Kv1.5 expression. Our results point to the possible link between Kv1.5 channel and the pathophysiological processes in EAE.
Coxiella burnetii is capable of causing a variety of acute and chronic infections. We present a case of pericarditis with serologically confirmed chronic C. burnetii infection. This case report ...emphasises the justification of serological testing for chronic C. burnetii infection in patients with prolonged or recurrent pericarditis, particularly in countries endemic for C. burnetii infection.
To get more insight into molecular mechanisms underlying oxidative stress and its link with insulin resistance, oxidative stress parameters, as well as, antioxidant enzyme activities were studied in ...young, non-obese women with polycystic ovary syndrome (PCOS). Study was performed in 34 PCOS women and 23 age and body mass index (BMI)-matched healthy controls. Plasma nitrotyrosine and malondialdehyde (MDA), representative byproducts of protein and lipid oxidative damage, were determined by enzyme immunoassay. Antioxidant enzyme activities, superoxide dismutase (SOD) and glutathione peroxidase (GPX) were studied spectrophotometrically. Insulin resistance was calculated using homeostasis assessment model (HOMA-IR). Plasma nitrotyrosine and MDA were increased, but only nitrotyrosine was significantly higher (p < 0.05) in PCOS women compared to controls. Uric acid (surrogate marker of × antine oxidase) was also significantly elevated in PCOS (p < 0.05). Both plasma SOD and GPX activity showed no statistically significant difference between PCOS and controls. Indices of insulin resistance (insulin and HOMAIR) were significantly higher in PCOS group and positively correlated with level of MDA (r = 0.397 and r = 0.523, respectively; p < 0.05) as well as GPX activity (r = 0.531 and r = 0.358, respectively; p < 0.05). Our results indicate that insulin resistance could be responsible for the existence of subtle form of oxidative stress in young, nonobese PCOS women. Hence, presence of insulin resistance, hyperinsulinemia and oxidative damage are likely to accelerate slow development of cardiovascular disease in PCOS.
Abstract
STUDY QUESTION
What are the most relevant factors associated with non-alcoholic fatty liver disease (NAFLD) in women with polycystic ovary syndrome (PCOS)?
SUMMARY ANSWER
Insulin resistance ...(IR) and lipid accumulation product (LAP) are independently associated with NAFLD in PCOS.
WHAT IS KNOWN ALREADY
Obesity and IR are frequently present in both women with PCOS and subjects having NAFLD. The coexistence of PCOS and NAFLD might synergistically increase the risk for both type 2 diabetes (T2DM) and cardiovascular disease (CVD). LAP, calculated from waist circumference (WC) and triglycerides (TGs) concentrations (WC-58) × TGs, has been shown to represent an integrated marker of cardiometabolic risk in women with PCOS.
STUDY DESIGN, SIZE, DURATION
This cross-sectional study included 600 Caucasian women diagnosed with PCOS by the Rotterdam criteria between May 2008 and May 2013.
PARTICIPANTS, SETTINGS, METHODS
The study was done at the university hospitals in Belgrade, Serbia and Thessaloniki, Greece. All subjects underwent anthropometric measurements and analyses of fasting blood glucose, insulin, lipids, total testosterone and SHBG, as well as liver tests (transaminases, γ-glutamyltransaminase, total bilirubin and alkaline phosphatase). Calculations for a NAFLD liver fat score (NAFLD-LFS) (with, accordingly, determination of metabolic syndrome and testing for T2DM) as well as homeostasis model assessment of IR (HOMA-IR), LAP as a marker of visceral adiposity, and free androgen index (FAI) were performed. We evaluated the prevance of NAFLD and analyzed associations of the above variables with NAFLD.
MAIN RESULTS AND THE ROLE OF CHANCE
NAFLD was more prevalent in patients with PCOS than in controls (50.6 versus 34.0%, respectively). Women with PCOS had higher readings for WC, LAP, insulin and HOMA-IR, total cholesterol and TGs than controls (P < 0.001). In PCOS women, the NAFLD-LFS significantly (P < 0.001) correlated with WC, BMI, glucose, HOMA-IR, TGs, LAP and FAI. In multivariate logistic regression, HOMA-IR and LAP were independently associated with NAFLD (P ≤ 0.001).
LIMITATIONS, REASONS FOR CAUTION
A possible weakness of the study may be the absence of structural confirmation of liver status. Hovewer, liver biopsy is invasive, difficult to perform in large populations and carries some risk of complications while magnetic resonance spectroscopy does not provide any information regarding the presence of fibrosis and is not routinely available. Another possible limitation could be the measurement of total testosterone by radioimmunoassay, which can be inaccurate when determining low levels of testosterone. Finally, fewer controls than subjects in the study group could have affected the significance of the results.
WIDER IMPLICATIONS OF THE FINDINGS
There is a debate on the most accurate clinical method for diagnosing liver disease as an early predictor of T2DM and CVD in general population and in PCOS women. There current study provided data on this issue from a cohort of Caucasian women with PCOS.
STUDY FUNDING/COMPETING INTEREST(S)
The study was supported by a research grant by the Serbian Ministry of Science and Education (grant nos 41009 and 175032). All authors have no competing interests.
This paper presents the problem of the hydropower plant oblique water inflow and its influence on the turbines operation. Oblique water inflow on the low head hydropower plant with bulb turbines ...influences turbine characteristics. The characteristics change occurs due to swirl incidence in the turbine inlet which spreads to the guide vanes inlet. Downstream, the flow conditions change is caused in the turbine runner in relation to the flow conditions without swirl inflow. Special attention is paid to the phenomenon of swirl flow incidence in the turbine conduit. With the aim of presenting and analyzing the oblique water inflow consequences on the hydropower plant operation, the existing turbine model tests results, performed in the laboratories, and the in situ prototype testing results have been used.
Molecular mechanisms underlying pathophysiology of polycystic ovary syndrome (PCOS), especially those related to cortisol signaling, are poorly understood. We hypothesized that modulation of ...glucocorticoid receptor (GR) expression and function, may underlie possible PCOS-related impairment of feedback inhibition of hypothalamic-pituitary-adrenocortical (HPA) axis activity and thus contribute to increased adrenal androgen production in women with PCOS.
24 normal-weight and 31 obese women with PCOS were compared to 25 normal-weight controls. Fasting blood samples were collected for measurements of serum concentrations of dehydroepiandrosterone sulfate, testosterone, sex hormone-binding globulin, insulin, basal cortisol and cortisol after oral administration of 0.5 mg dexamethasone. Concentrations of GR mRNA, GR protein, mineralocorticoid receptor (MR) protein and heat shock proteins (Hsps), as well as the number of GR per cell (B(max)) and its equilibrium dissociation constant (K(D)) were measured in isolated peripheral blood mononuclear cells.
An increase in HPA axis sensitivity to dexamethasone, an elevation of the GR protein concentration, and unaltered receptor functional status were found in both normal-weight and obese women with PCOS vs. healthy controls. Lymphocyte MR, Hsp90 and Hsp70 concentrations, and MR/GR ratio were similar in all groups. Correlation between B(max) and K(D) was weaker in the group of obese women with PCOS than in the other 2 groups.
The results did not confirm the initial hypothesis, but imply that PCOS is associated with increased GR protein concentration and HPA axis sensitivity to dexamethasone.
Nitric oxide synthases (NOSs) and Na(+)/K(+)-ATPase are enzymes essential for regular functioning of the heart. Since both enzymes are under insulin and androgen regulation and since insulin action ...and androgen level were disturbed in polycystic ovary syndrome (PCOS), we hypothesized that cardiac nitric oxide (NO) production and sodium/potassium transport would be deteriorated in PCOS. To test our hypothesis we introduced animal model of PCOS based on dihydrotestosterone (DHT) treatment of female Wistar rats and analyzed protein expression, phosphorylation or subcellular localization of endothelial NOS (eNOS), inducible NOS (iNOS) and alpha subunits of Na(+)/K(+)-ATPase in the heart. Obtained results indicate that DHT treatment significantly decreased cardiac eNOS protein level and activating phosphorylation at serine 1,177, while inhibitory phosphorylation at threonine 495 was increased. In contrast to expression of eNOS, iNOS protein level in the heart of DHT-treated rats was significantly elevated. Furthermore, cardiac protein level of alpha 1 subunit of the ATPase, as well as its plasma membrane content, were decreased in rats with PCOS. In line with this, alpha 2 subunit protein level in fraction of plasma membranes was also significantly below control level. In conclusion, DHT treatment impaired effectiveness of NOSs and Na(+)/K(+)-ATPase in the female rat heart. Regarding the importance of NO production and sodium/potassium transport in the cardiac contraction and blood flow regulation, it implicates strong consequences of PCOS for heart functioning.
Experimental approaches for identifying T-cell epitopes are time-consuming, costly and not applicable to the large scale screening. Computer modeling methods can help to minimize the number of ...experiments required, enable a systematic scanning for candidate major histocompatibility complex (MHC) binding peptides and thus speed up vaccine development. We developed a prediction system based on a novel data representation of peptide/MHC interaction and support vector machines (SVM) for prediction of peptides that promiscuously bind to multiple Human Leukocyte Antigen (HLA, human MHC) alleles belonging to a HLA supertype. Ten-fold cross-validation results showed that the overall performance of SVM models is improved in comparison to our previously published methods based on hidden Markov models (HMM) and artificial neural networks (ANN), also confirmed by blind testing. At specificity 0.90, sensitivity values of SVM models were 0.90 and 0.92 for HLA-A2 and -A3 dataset respectively. Average area under the receiver operating curve (
A
ROC) of SVM models in blind testing are 0.89 and 0.92 for HLA-A2 and -A3 datasets.
A
ROC of HLA-A2 and -A3 SVM models were 0.94 and 0.95, validated using a full overlapping study of 9-mer peptides from human papillomavirus type 16 E6 and E7 proteins. In addition, a large-scale experimental dataset has been used to validate HLA-A2 and -A3 SVM models. The SVM prediction models were integrated into a web-based computational system MULTIPRED1, accessible at
antigen.i2r.a-star.edu.sg/multipred1/.
Aim: The aim of the study is the detection of primary and metastatic neuroendocrine tumors using super(111)In pentetreotide (OctreoScan), which is a long-acting analog of somatostatin. Patients and ...Methods: A total of 30 patients was investigated. Scintigraphy of the whole body, (and tomography 360 degree /6 degree if necessary) was performed 4h - 48 h after i.v. administration of 111MBq super(111)In pentetreotide. Results: In the group with 12 neuroendocrine carcinomas of unknown origin, there were 10 true positive (TP) findings (6 with liver metastases, one with liver, lung, and bone metastases, one with liver and mediastinal lymph node metastases and 2 with liver and retroperitoneal lymph node metastases), while 2 were false negative (FN) (poorly differentiated carcinoma with retroperitoneal metastases). In 6 patients scintigraphy influenced further patient management. From the group of 12 pancreatic neuroendocrine tumors, in 8 neuroendocrine pancreatic carcinomas, there were 6 TP (4 with liver metastases) and 2 FN (poorly differentiated). In 2 patients with pancreatic gastrinomas findings were TP, while in 2 patients with insulinoma one was TP and in the other TN. In 6 patients scintigraphy influenced further patient management while in 4 only contributed. From the group of 6 neuroendocrine lung tumors there were 4 TP (4 patients with bronchial carcinoid, two with liver metastases and the other two with liver, lung and bone metastases), in 1 patient with atypical lung carcinoid after surgery, findings were TN, while in one with neuroendocrine lung tumor (ACTH secreting) it was FN (small mediastinal tumor. In 2 patients scintigraphy influenced further patient management while in 2 only contributed. Because of the high uptake of radiopharmaceutical, and widespread metastases, six patients were indicated for radionuclide therapy with super(90)Y-DOTA TATE, and three of them received it. Conclusion: Preliminary results show that scintigraphy of neuroendocrine tumors is a useful method in diagnosis, staging and follow up of the patients suspected to have neuroendocrine tumors in the lungs. It is also helpful in the appropriate choice of therapy, including radionuclides.
PDF
