bluuebunny/crossref_metadata_2025 huggingface dataset:
Immunochistochemical characteristics of blood vessels in non-visualized and visualized on MRI pituitary adenoma in patients with Cushing’s disease
Authors: Khandaeva Patimat M. , Voronkova Ija А. , Belaya Zhanna E. , Rozhinskaya Ljudmila Ya. , Vorontsov Aleksandr V. , Grigoriev Andrej Ya. , Mel’nichenko Galina A.
Published: October 2016

Background. Regardless of improvements in MRI, up to 20% of ACTH-secreting pituitary tumors are only identified at surgical exploration. Aim. Тo estimate whether there is any difference in blood vessels and the subsequent ability to uptake contrast agent in visualized microadenoma as compared to non-visualized on MRI ACTH-secreting pituitary tumors.Material and methods. Retrospective evaluation of ACTH-positive pituitary tumors from patients with Cushing’s disease (n=39) with either non-visualized pituitary tumor on MRI (n=17) or pituitary tumor less then 25 mm (n=22). MRI was performed using Siemens Magnetom Harmony 1.0T with gadolinium. Selected tumors were stained with anty-СD34 antibody (clone QBEnd/10, RTU, Leica) and anty-D2-40 antibody (clone D2-40, RTU, Dako). We evaluated the microvessels density and measured the diameter of larger and smaller vessel.Results. The microvessels density were not different in subject with visualized [123 (77; 136)] and non-visualized [112 (110,0; 126,5)] pituitary adenomas as well as number of slit-shaped vessels [32 (5; 50) in visualized vs 25 (5; 50) in non-visualized pituitary adenoma]. The diameter of these vessels also did not differ: the diameter of the largest vessels in patients without visualization 53 µm (32,5; 63,5) vs 33 µm (30,0; 51,5) the average diameter of the blood vessels 15 µm (14,5—26,0) against 13 µm (12; 14).Conclusions. The diameter and microvessels density in ACTH-producing pituitary adenoma does not affect the visualization of adenoma on MRI in patients with Cushing ‘s disease.
Russian Association of Endocrinologists recommendations for diagnosis, treatment and prevention of vitamin D deficiency in adults
Authors: Pigarova Ekaterina A. , Rozhinskaya Ludmila Ya. , Belaya Janna E. , Dzeranova Larisa K. , Karonova Tatiana L. , Ilyin Alexanrd V. , Melnichenko Galina A. , Dedov Ivan I.
Published: October 2016

Background. Adequate intake of vitamin D and its concentration in serum is important for the health of bones and calcium-phosphorus metabolism and for the optimal functioning of many organs and tissues. Most epidemiological studies have shown that vitamin D deficiency is widespread among the population in Russian Federation.Material and methods. We reviewed relevant literature on the epidemiology of insufficiency and deficiency, skeletal and extraskeletal effects of vitamin D and summarized recommendations for the diagnosis, prevention and treatment of vitamin D deficiency in the general population, which were subsequently discussed and amended in conjunction with leading endocrinologists of the Russian Federation who are experts in this subject.Results. The optimal concentration of 25(OH)D in the serum as the best indicator of vitamin D body stores is recognized as 30—100 ng/ml (75—250 nmol/l), insufficiency — from 20 to 30 ng/ml (50 to 75 nmol/l), deficiency — less than 20 ng/ml (less than 50 nmol/l). In prevention and treatment it is recommended to stick to the target serum levels of 25(OH)D in the range of 30—60 ng/ml (75—150 nmol/l). We’ve developed a general practice recommendations for the prevention, diagnosis and treatment of vitamin D deficiency in adults, including pregnant and lactating women, persons over 50 years old and subjects suffering from various diseases affecting the metabolism of vitamin D.Conclusions. Increased sufficiency of vitamin D in the population should be included as one of the priorities of modern healthcare due to proven preventive health effects on the musculoskeletal system and the potential positive impact on many socially significant diseases. This publication is a detailed version of the Federal Guideline.
Clinical correlates of thrombodynamics in men with metabolic syndrome: the impact of insulin resistance
Authors: Pchelin Ivan Y. , Hudiakova Natalia V. , Shishkin Alexander N.
Published: October 2016

Background. Hypercoagulation is one of the cardiovascular risk factors in patients with metabolic syndrome (MS). It results from various factors including hyperhomocysteinemia, endothelial dysfunction, non-enzymatic glycation of proteins etc.The aim of this study was to assess clinical correlates of thrombodynamics in insulin resistant and non insulin resistant men with metabolic syndrome.Methods. We investigated 79 patients with MS diagnosed in accordance with IDF criteria (2009). The main group consisted of 44 men with MS including insulin resistance. The control group consisted of 35 men with MS not including insulin resistance. In addition to routine clinical tests we performed thrombodynamics assay and measured serum levels of asymmetric dimethylarginine (ADMA) and homocysteine. Mann-Whitney U-test and Spearmen’s correlation coefficient (rs) were used for statistical analysis.Results. There was no significant difference between thrombodynamics parameters, ADMA and homocysteine levels between the two groups. In both groups thrombodynamics parameters had no correlations with body mass index, hemoglobin level, platelet count and serum ADMA level. In patients with insulin resistance clot density correlated positively with serum level of C-reactive protein (rs=0.621, p=0.007); average and initial rates of clot growth correlated positively with homocysteine level (rs=0.539, p=0.017, and rs=0.554, p=0.014, respectively). In patients with insulin resistance clot density and rates of clot growth were not interrelated with the above mentioned parameters.Conclusions. The results of the study suggest that insulin resistant men with MS are characterized by clinical correlates between thrombodynamics parameters, homocysteine and C-reactive protein levels while patients without insulin resistance have other, unestablished determinants of clot density and rates of clot growth.
Advanced glycation end products, fibroblast growth factors and the development of atherosclerosis in patients with diabetes
Authors: Ivannikova Ekaterina V. , Kalashnikov Victor Y. , Smirnova Olga М.
Published: October 2016

Introduction. Atherosclerotic processes are more pronounced at diabetes mellitus (DM). Chronic hyperglycemia activated pathological mechanisms of restructuring the connective tissue, including the vascular wall. Fibroblasts are the main cellular components. Activation of the transforming growth factor (TGFß1), basic fibroblast growth factor (ß-FGF), produced by fibroblasts, inflammatory markers (interleukin-6 (IL-6), tumor necrosis factor (α-TNF), advanced glycation endproducts (AGE) and their receptors (rAGE), may have important prognostic value.Objective. To investigate the level AGE, TGFß1 and ß-FGF in patients with severity atherosclerosis coronary artery disease (CAD), to compare with normal blood glucose and DM.Material and methods. The study involved two groups of patients with CAD: 56 patients of the first group had normal blood glucose and 78 patients suffered from DM type 2. The degree of coronary atherosclerosis was determined by coronary angiography (CAG) in all patients. The blood samples were collected from the aorta during CAG and cubital vein simultaneously, immediately centrifuged (15000g*min), supernatants were stored at –70*C until analysis were done. Serum was analyzed by ELISA (IFA). The critical significance level (p) for statistical hypothesis testing was set at <0.05.Results. Average β-FGF, TGF-ß1, AGE, RAGE in the second group was significantly higher than in the first (p<0.005). Increased level of the AGE, RAGE and TGFß1 was positive correlated with low-density lipoprotein and triglycerides (R=0,049, p<0.005). IL-6 was significantly higher in the second group. There was the significant correlative relationship between the levels AGE, RAGE, TGFß1, ß-FGF and IL-6 with DM duration (R=-0,120; p=0.009), direct association with HbA1C (R=0,429; p=0.006). There were significantly higher level of the AGE, TGFß1 and ß-FGF in aortic blood than in peripheral venous blood p<0,005). IL-6 level had opposite features: serum IL-6 was higher in venous than arterial blood. The patients with DM had three-vessel disease often (73%) then the patients without DM (R = 0,021, p<0.005), which was direct correlated with level TGFß1 (R = 0,03, p<0.005). There weren`t any differences in α-TNF level between two groups.Discussion. High AGE, TGFß1 level and positive correlation with atherogenic lipids may indicate the role of the connective tissue remodeling in pathogenesis of the coronary atherosclerosis. As the longer DM duration led to increasing AGE, TGFß1 and IL-6 levels the chronic hyperglycemia can restructure the vascular wall. Higher AGE, TGFß1 and ß-FGF levels in aorta then in peripheral blood may show the involvement of the cardiomyocytes in these growth factors metabolism.Conclusion. DM existence with CAD was characterized by higher AGE, RAGE, TGFß1 and IL-6 levels, which was direct correlated with the atherogenic lipids. Patients with type 2 DM and CAD had more severe coronary artery disease.
The facial expression of emotions recognition in patients with polycystic ovary syndrome
Authors: Czyzyk Adam , Polak Kinga , Podfigurna Agnieszka , Kozlowski Stanislaw , Meczekalski Blazej
Published: October 2016

Background. A facial expression of emotions recognition is one of the basic psychological abilities. Sex steroids are able to strongly modulate the process of interpretation of facial expressions, as it has been shown in Turner syndrome patients.Objective. The aim of this study was the assessment of ability to interpret the facial emotions in women with polycystic ovary syndrome (PCOS).Methods. Participants completed a visual emotional task in which they were asked to recognize the emotion expressed of 80 randomly chosen facial expressions from NimStim set (Tottenham et al., 2009). With dedicated software we were able to assess the accuracy of patients facial emotion recognition (in comparison to NimStim validation set) and time required to provide the answer. Patients with psychotic personality have been excluded using Eysenck Personality Questionnaire (EPQ). All the patients underwent also hormonal tests including gonadotropins, estradiol and androgen concentrations.Patients. 80 women diagnosed with PCOS and hyperandrogenemia were included to the study. The control group consisted of 60 healthy, euovulatory women matched by age.Intervention. Each patient underwent visual emotional and EPQ tasks using specifically designed software.Main outcome measures. The accuracy rate (AR) and time required to recognize emotion (TE) of following emotions: anger, disgust, fear, happiness, sadness, surprise, calm and neutral has been measured.Results. Patients with PCOS showed significantly reduced AR for calm (0.76¬+/-0.09) and surprise (0.67+/-0.18) emotions in comparison to controls (0.81+/-0.09, 0.79+/-0.08 respectively). The TE for the anger was higher in PCOS group. Estradiol concentrations showed a statistic tendency (p=0.07) for correlation with TE for the happiness in controls. Conclusions. In this study we showed for the first time that patients affected by hyperandrogenism shows signs of disturbed recognition of facial expression of emotions.
Lipodystophic laminopathies are characterised by an increased intra/whole abdominal fat ratio with preserved fat/lean mass ratio and hypoleptinemia, in contrast with obese people, compared to controls
Authors: Le Mapihan Kristell , Benomar Kanza , Espiard Stéphanie , Vahe Claire , Ernst Olivier , Vigouroux Corinne , Lion Georges , Douillard Claire , Vantyghem Marie-Christine
Published: October 2016

Introduction. The diagnosis of non-HIV lipodystrophies is challenging, especially since borderline forms with type 2 diabetes have been described (Strickland Diabetes Care 2013).Aim: to identify the most specific anthropometric and biological parameters enabling to differentiate lipodystrophic from obese and control subjects.Methods. This prospective study (clin.gov 2009-AO-1169-48) included 94 patients divided in 3 groups adjusted for age and gender: 52 lipodystrophic patients (among whom 16LMNA–mutated lipodystrophies (LDM),16non-LMNAmutated partial lipodystrophies (LDNM), and 20 other types of lipodystrophies), 28 obese (O; 12 diabetic (OD) and 16 non-diabetic (OND)) and 14 normal-weighed healthy subjects (C). The anthropometric (DEXA, MRI) characteristics and leptin levels of the patients were recorded. Three ratios were calculated to assess the respective part of fat and lean mass (FM/LM), intra- and whole abdominal fat (IAF/WAF) and adipose tissue function (leptin/WAF).Results. The three groups differed by the FM, LM, IAF, WAF, leptinemia, trunk FM/LM (P<0.0001), IAF/WAF (P<0.001) and leptin/WAF (P<0.01). The main distinctive feature of LDM compared to C was IAF (188±38vs 82±23 cc;P<0.01) whereas BMI, FM, LM, WAF and leptinemia were similar. The ratios ranges of the five subgroups were as follows: IAF/WAF: 0.5 in LDMvs0.3 in all other subgroups; trunk FM/LM: 0.2 in LDM and C, increased from 0.5 to 0.7 and 0.8 respectively in LDNM, OD, OND); leptin/WAF: decreased to 2.3 and 1.6 in respectively LDM and LDNM compared to C (2.7), and increased in OD (3.7) and OND (5.6).Conclusion. Increased intra/whole abdominal fat ratio, hypoleptinemia and preserved fat/lean mass ratio characterized lipodystrophic laminopathies, in contrast with obese people who showed an increased fat/muscle mass, hyperleptinemia and preserved intra/whole abdominal fat ratio. Non-mutated lipodystrophic patients were intermediate, with decreased leptin/WAF ratio, close to LDM, and increased IAF/WAF and FM/LM ratios close to the obese population.
Hippo Pathway mediator TAZ acts as a negative regulator of the sodium iodide symporter
Authors: Fernández-Méndez Celia , Santisteban Pilar
Published: October 2016

Background. TAZ/WWTR1 (transcriptional coactivator with a PDZ-binding domain) is a transcriptional cofactor involved in the Hippo Signalling pathway, which is described to have a key role in the control of cell proliferation, apoptosis, the inhibition of cell-cell contact, stem cell self-renewal and tissue regeneration. TAZ has been reported to regulate these processes through the transactivation of transcription factors in the nucleus, where it has also been shown to interact with Smad2/3-Smad4 complexes favouring nuclear accumulation under TGFβ stimulation. TAZ co-activates Pax8, a master gene of thyroid differentiation, within the thyroglobulin promoter. Furthermore, Pax8 is the main positive regulator of sodium iodide symporter (NIS) expression and it has been reported to interact with Smad3 causing NIS transcriptional repression mediated by TGFβ.Aim. Therefore, the aim of this work was to study the involvement of TAZ in the expression of NIS, since it is an important protein not only for the correct function of the thyroid gland, but also for radioiodide treatment in thyroid cancer.Methods and Results. Strikingly, we observed that TAZ negatively regulates the transcriptional activity of Pax8 within the NIS promoter. Furthermore, we provided evidence that TAZ could play an important role in the downregulation of NIS expression by TGFβ; we detected that TAZ protein is mainly located in the nucleus under treatment with this cytokine and its silencing induces a partial recovery of NIS protein and mRNA levels. Our results also demonstrated an increased expression of TAZ in thyroid carcinoma cell lines, in which NIS levels are typically decreased. Specifically, TAZ nuclear translocation is increased in those thyroid carcinoma cells with mutated BRAFV600E or when this oncogene is conditionally activated. Since we have described that this mutation increases the secretion of TGFβ, this could be connected with the decreased levels of NIS in these cells.Conclusion. This study has shed light on the important role of the Hippo pathway in the regulation of NIS expression in thyroid cells, repressing Pax8 activity and impaired thyroid differentiation. Given that this protein has been identified to be overexpressed in thyroid carcinoma, future research of the role of TAZ in thyroid tumorogenesis will enable development of new strategies to treat thyroid cancer.
Erk dimers inhibition is a therapeutic target in thyroid cancer
Authors: Acuña-Ruiz Adrián , Zaballos-Sánchez Miguel , Riesco-Eizaguirre Garcilaso , Santisteban Pilar , Crespo P.
Published: October 2016

Thyroid carcinoma is the most common endocrine malignancy, and its incidence is rapidly rising in the world. Its initiation and progression involves multiple genetic and epigenetic alterations whereby BRAF and RAS mutations lead to the activation of the ERK signaling pathway. Recently, significant advances have been accomplished by developing pharmacological agents directed against the kinases of the RAS-ERK pathway. However, most of the molecules tested have undesired side effects and promote drug resistance. Consequently, it is imperative to find alternative RAS-ERK pathway inhibitors. It has been shown that by inhibiting ERKs dimerization it is possible to suppress tumor progression. DEL22379, a small molecule inhibitor for ERK dimerization, has been identified to impede the growth of melanoma tumor cells driven by RAS-ERK pathway oncogenes, without affecting ERK phosphorylation (Cancer Cell 28:17082 2015). The aim of this work is to study the role played by ERK dimerization and its inhibition using DEL22379 in thyroid cancer progression. We have used an in vitro model of thyroid tumor cells harboring oncogenic drivers (RAS or BRAF) to complete viability, migration and invasion assays as well as an orthotopic mouse model with anaplastic cells as an in vivo model. We observed that in BRAF mutated cells, ERK dimer formation is sustained for longer compared to the RAS mutated or control cells, resulting in the altered activation of the effected signaling pathway. RAS mutated cells are resistant to DEL22379 in vitro, while BRAF mutated cells are not able to form ERK dimers upon inhibitor addition. Consequently, these cells lose their invasive and migratory potential as well as displaying low viability. Preliminary results suggest DEL22379 treatment inhibits tumor growth in orthotopic mice. These results describe a new molecule that could be effectively used as a therapy in thyroid cancers harboring BRAF or RAS mutated genes. We have observed it is able to partially revert the tumorigenic phenotype, which may result in an improved prognosis in thyroid cancer patients.
Correlation of Morphological and Functional Characteristics of Growth Hormone-Producing Pituitary Adenomas
Authors: Panteleeva Evgeniya S. , Ilovayskaya Irena A. , Stashuk Galina A. , Dreval Alexandr V.
Published: October 2016

Introduction. Previous studies demonstrated a relationship between T1- and T2-weighted signal intensity and tumor growth patterns and potential as well as hormonal activity in somatotropinomas. Further investigation of these findings could serve to define predictive diagnostic and treatment factors based on MRI characteristics.The aimof this retrospective study was to analyze the MRI characteristics of growth hormone-producing pituitary adenomas in newly diagnosed patients with acromegaly and to compare them with the corresponding morphological and biochemical characteristics.Methods. Seventy five patients with newly acromegaly were included in the study. Pre-treatment T1- and T2-weighted MR-images of all patients were analyzed, taking into account the intensity of the signals produced by the tumors, as well as their dimensions and growth direction. Growth hormone and IGF-1 levels were also recorded.Results. Out of 75 patients, 74.7% were macroadenomas. T1-weighted adenoma signal was hypointense in 45.3% of patients, hyperintense in 18.7% of patients and isointense in all other cases. T2-weighted adenoma signal was hypointense in 32.3% and hyperintense in 40.5% of patients. No statistically significant differences were found between GH and IGF1 levels as well as signal intensity in relation to patient age. Inferior tumor extension was present in 60.0% of patients overall and 33.3% more prevalent in patients with hyperintense T2 signal and 24.5% and 11.7% more prevalent in patients with hypointense and hyperintense T1 signal respectively. Superior extension was observed in 46.7% of patients and did not differ significantly from inferior extension in patients with hypointense T2 signal. The highest levels of IGF1 were associated with superior extension, while the highest levels of GH were associated with inferior extension. Mean adenoma volume was 8.45 times higher and GH levels were 3.8 times higher in patients with hyperintense T2-weighted signal and 2.3 and 1.3 times higher respectively in patients with hyperintense T1-weighted signal.Conclusion. Hyperintense T1- and T2-weighted MRI signal was associated with larger tumor dimensions, increased GH levels and more frequent inferior extension, all of which indicate higher proliferative potential of the adenomas.
Endocrine disorders with craniopharyngioma in adults before and after surgery
Authors: Klochkova Irina S. , Astafieva Lyudmila I. , Konovalov Alexsander N. , Kalinin Pavel L. , Kutin Maksim A. , Fomichev Dmitriy V. , Sharipov Oleg I.
Published: October 2016

Background. Craniopharyngiomas (CF) - a benign tumor of the embryologic origin. The surgical method of treatment is basic.Aim: to estimate dynamics of endocrine disorders before and after surgical treatment of CF at different topographical variations.Methods.The research involved 42 patients older than 18 years (25 women and 17 men) with a mean age - 41 [21; 69] with a verified diagnosis of CF. All patients were operated in 28 cases – total resection, in 7 - the pituitary stalk was saved. Before and 6 months after the surgery all patients were examined by means of hormonal blood tests (TSH, free T4, cortisol, prolactin, LH , FSH, estradiol, testosterone, IGF-1). By tumor localizing patients were divided into 4 groups: 1 – intra-suprasellar (2) 2 – at location of the pituitary stalk (15), 3 – combined «the pituitary stalk» and ventricular (10), 4 –intra-ventricular (15).Results. In group 1: panhypopituitarism -2 (100%), diabetes insipidus (DI) – 0. Both patients had subtotal ablation. After the surgery the nature of disturbance has not changed. In group 2: secondary hypoadrenalism - 9 (60%), hypothyroidism - 11 (73%), hypogonadism - 12 (80%), DI - 7 (46%), hyperprolactinemia - 9 (60%). After the surgery panhypopituitarism - 15 (100%), DI - 14 (93%), hyperprolactinemia - 4 (26 %). In group 3: secondary hypoadrenalism - 3 (30%), hypothyroidism - 6 (60%), hypogonadism - 6 (60%), DI - 2 (20%), hyperprolactinemia - 3 (30%). After the surgery panhypopituitarism - 10 (100%), DI - 10 (100%), hyperprolactinemia - 3 (30 %). In group 4: secondary hypoadrenalism - 6 (40%), hypothyroidism - 9 (60%), hypogonadism - 12 (80%), DI - 5 (33%), hyperprolactinemia - 8 (53%). After the surgery panhypopituitarism - 10 (71%), secondary hypoadrenalism - 12 (85%), hypothyroidism - 13 (92%), hypogonadism - 11 (79%), DI - 11 (78%), hyperprolactinemia - 8 (53%).Conclusion. The high incidence of endocrine disorders is caused by the localization of the CF with predominance of secondary hypogonadism and hypothyroidism. After the surgery worsening hormone deficiency was mentioned, also while preserving the pituitary stalk. Non-radical ablation of ventricular CF can partially maintain endocrine function.
Carbohydrate metabolism in patients with Cushing disease: a glance at the incretin system
Authors: Matchekhina Lubov V. , Shestakova Ekaterina A. , Belaya Zhanna E. , Shestakova Marina V.
Published: October 2016

Introduction. The relevance of carbohydrate metabolism studying in patients with Cushing disease can be explained by frequent occurrence of glucose metabolism disturbances on the one hand, and difficulties in glucose-lowering therapy in these patients on the other. The effectiveness of hyperglycaemia treatment may be reduced due to difficulties in remission / cure of the underlying disease, as well as to the use of specific drug-therapy, leading to the hyperglycaemia. There is a growing interest in research aimed at studying the role of incretin system in the pathogenesis of secondary hyperglycemia associated with neuroendocrine diseases recently.Methods. A total of 20 patients with Cushing disease were included, (19 female and 1 male), the mean age was 37.5 years (18-69). All of the patients were diagnosed with Cushing disease for the first time (using urinary free cortisol levels and MRI-data); none of them had a history of previous drug therapy, radiotherapy or pituitary surgery. The mean HbA1c level was 5,8% (5,3-6,2). All patients underwent OGTT, during which glucose, glucagon, GLP1, GLP2, GIP, ghrelin were measured at 0, 30 and 120 min respectively. The control group included 21 patients without previous history of carbohydrate metabolism disturbances. After OGTT 57% were presented without any carbohydrate metabolism disturbances, 28,57% presented with prediabetes and 14,43% were diagnosed with diabetes.Results. After glucose levels analyzing 40% of patients were diagnosed with early carbohydrate metabolism disturbances ,15% were diagnosed with diabetes. After glucose intake a slight inrease in glucagon levels with a peak by 30’ (p=0,001) compared to gradually decreasing levels in controls was observed . The levels of GIP during OGTT were not significantly different compared to control group. GLP-1 and GLP-2 levels were significantly higher compared to controls (p=0,017 and p<0,001 respectively) with peak levels at 30’. Ghrelin levels were also significantly higher compared to controls (p=0,013)Conclusion. Incretins levels can be possible markers of specific carbohydrate metabolism disturbances in patients with Cushing disease and presumably will help to differentiate steroid diabetes from T2DM. Further investigations needed to prove these speculations.
Clinical manifestations of hypercortisolism in patients with adrenal Cushing’s
Authors: Budul Natalia A. , Komerdus Irina V. , Dreval Alexandr V. , Chekanova Anastasia V.
Published: October 2016

Aim: to evaluate clinical manifestations of hypercortisolism in patients with adrenal Cushing’s (ACush).Material and Methods. 32 patients (30 (93.7%) female, 2 (6.3%) male, 41.5 [32.2; 54.0] y.o. with ACush.Results. Adenoma was found in right adrenal in 37.5% of patients, in left – 40.6%, bilateral adenomas in 21.9%. Maximum size of adenoma was 3.3 [3.0;4.2] cm. Level of UFC was 654.1 [383.0;1153.0] nmol/l/h, ACTH – 1.1 [1.1;2.3] pmol/l, serum cortisol after 1-mg overnight dexamethasone suppression test– 644.0 [431.5;710.5] nmol/l. Features that best discriminate Cushing’s syndrome were found not in all patients - proximal muscle weakness - in 81.3%, facial fullness -75.0%, easy bruising - 56.2% and striae - 43.7%. The most frequent (≥80%) complains were weight gain (87.5%), fatigue (84.3%), headache (50-80%). In <50% - poor skin healing, prolonged wound healing, depression, menstrual abnormalities etc. Arterial hypertension diagnosed in 31/32 patients, systolic BP before treatment was 180 [170;220] mm Hg, diastolic BP - 100 [100;110] mm Hg. Antihypertensive therapy: one medication received 5 patients (16.1%), two – 8 (25.8%), three - 12 (38.7%) , four – 1 (3.2%), without therapy - 5 (16.1%). Hypokaliemia were in 26.6%, hypercholesterolemia - 86.6%. In 9 patients diabetes mellitus (DM) diagnosed before diagnosis ACush was made. 75-g OGTT performed in 16 patients without known DM thereafter DM was diagnosed in 2 (12.5%), IGT (impaired glucose tolerance) in 6 (37.5%). Bone densitometry performed in 20 patients: in 5 of them osteoporosis was diagnosed (15.6%), in 5 -osteopenia (15.6%), normal bone density – in 10 (31.2%). Pathological fractures (vertebral, rib fractures etc) were in 3/5 osteoporotic patients.Conclusions. The most frequent complaints (≥80%) were weight gain, fatigue and proximal muscle weakness. Hypertension and hypercholesterolemia were in 96.9% and 86.6% patients. Diabetes and IGT in 53.1%, hypokaliemia (26.6%), osteoporosis (15.6%).
Microalbuminuria in primary aldosteronism
Authors: Rebrova Dina , Rusakov Vladimir , Krasnov Leonid , Vorokhobina Natalya , Sleptsov Ilya , Chernikov Roman , Fedorov Elisey , Sablin Ilya , Isheyskaya Maria
Published: October 2016

Background. Primary aldosteronism (PA) is an adrenal disorder which is characterized by the overproduction of the mineralocorticoid hormones by the adrenal glands when not as a result of excessive renin secretion. Different studies report the prevalence of PA in from 7 to 15 % patients with hypertension. Nowadays PA is considered to be the most frequent cause of secondary hypertension taking up to 30% of it. The importance of case detection of PA among hypertensive patients is not a matter of controversy presently. It has been demonstrated recently that patients with PA are more prone to cardiovascular events and target organ damage than essential hypertensive patients.Aim: to establish renal dysfunction in PA.Methods. We evaluated 192 low-renin hypertensive patients and 30 normotensive subjects. The mean age of the hypertensives was 47,5±3,4 years. The control group was 51,8±4,2 years old. PA was established in 57 patients, all the others were classified as low-renin essential hypertensives (LREH). Both groups were similar with respect to age (44,7±4,2 in PA, 48,3±3,9 in LREH), sex (female 63% of PA and 67% of LREH) and blood pressure (158±16/96±8 mm Hg in PA, 164±21/99±13 mm Hg in LREH). There were slight differences in BMI (31,4±4,3 in PA and 28,7±3,5 in LREH, p<0,05). PA and LREH patients significantly differed with respect to prevalence of diabetes mellitus (26,3% in PA and 9,6% in LREH, p<0,01) and duration of hypertension (7±5 years in PA and 13±4 in LREH, p<0,05).Results. We observed an increase in urinary protein excretion in both group. But in group of patients with PA it was higher than in LREH (0,14±0,06 vs. 0,05±0,03 g/24 h, p<0,05). In addition, patients with PA had higher serum creatinine concentrations (101,7±13,2 vs. 83,4±9,1 mkmol/l, p<0,05). Subgroup analyses of normoglycemic subjects showed that PA patients still had a higher creatinine concentration (84,3±11,8 vs. 81,9±10,5 mkmol/l) but the difference was no longer statistically significant. Although, microalbuminuria was significantly higher in non-diabetic PA patients (0,12±0,04 vs. 0,05±0,07 g/24 h, p<0,05). Diabetic subjects in both groups did not differ significantly with respect to microalbuminuria.Conclusions. Cross-sectional Primary Aldosteronism Prevalence in Italy (PAPY) study showed an increased prevalence of microalbuminuria in PA. The data from German Conn’s Registry showed a significant increase of serum creatinine concentrations in patients with PA but they did not observe any significant differences in protein excretion. In our study the differences in creatinine concentration were diabetes-dependent. Although, we suppose an increase of microalbuminuria in patients with PA to be aldosterone-dependent. However, this hypothesis should be confirmed in wider populations.
A new mutation in thyroid hormone resistance
Authors: Martins Ana Filipa , Martins João Martin , Do Vale Sónia , Miltenberger-Miltenyi Gabriel
Published: October 2016

Introduction. Thyroid Hormone Resistance (THR) is a rare syndrome with a variable and fluctuating clinical course depending on complex genetic and molecular defects.Case report. SCPR, a caucasian female patient aged 23, was referred to outpatient endocrine department because of increased T4 levels. There was no evidence of thyroid dysfunction or goiter. Past medical history was negative with normal growth and neurophysiological development and regular menstrual cycles. There was no family history of thyroid disease. Analytical evaluation revealed T4 – 17.9 µg/dL [Reference Value (RV): 4.5-12.5], T3 – 247 ng/mL (RV: 72-170), TSH – 4.9 µU/mL (RV: 0.4-4.0), FT3 – 7.8 pg/mL (RV: 1.8-4.2), FT4 – 2.6 ng/dL (RV: 0.8-1.9), TPOAb 11 U/mL (RV: <35), TgAb < 20 U/mL (RV: <40), TRAb < 1 (RV: <2). The TRH test (200 µg, ev) revealed a normal but high TSH response up to 23 µU/mL (5-25) and a sellar NMR scan showed no abnormalities. No medical treatment was prescribed. Over the follow up period of 10 years thyroid function fluctuated with borderline high FT4 and TSH. Clinical course was marked by the development of obesity, depressive syndrome and the diagnosis of chronic fatigue syndrome with two uneventful pregnancies. Over that period, either Hyperthyroidism or Hypothyroidism were diagnosed and treated at other institutions. Recently genetic testing revealed a new mutation on exon 10 of the β thyroid hormone receptor form c790G>T (p.Val264Phe) with unknown significance.Discussion. Several important points are illustrated by this case. 1) thyroid function tests may fluctuate over time, only sometimes with clear evidence of THR. 2) clinical manifestations of the syndrome are multiform and the relation to thyroid hormone levels is far from clear with abnormalities of growth and neurophysiological development, infertility, obesity, psychiatric disorders or subtle symptoms suggesting thyroid dysfunction variably reported; 3) interpretation of analytical abnormalities may be difficult with thyroid dysfunction commonly misdiagnosed; 4) medical treatment is controversial; 5) More than 100 mutations have been reported and the particular complexity of thyroid hormone effects – several isoforms of the receptor, homo- or heterodimerization of the receptor with the retinoid X receptor and dominant negative effects making the interpretation of the functional significance of new mutations difficult.
Association between emotional eating and BMI in patients with type 2 diabetes
Authors: Balkhiyarova Zhanna R , Avzaletdinova Diana S , Morugova Tatyana V , Sharipova Leisan F , Amankwah-Poku Margaret , Nouwen Arie
Published: October 2016

Background. Obesity mainly caused by overeating is one of the most important risk factor of type 2 diabetes mellitus (T2DM). The aim of the present study was to investigate eating behavior types of patients with T2DM and obesity.Methods. We compared samples of patients with T2DM from the UK (N=113, 64 men) and Russia (N=200; 61 men) whom we asked to complete the Dutch Eating Behaviour Questionnaire (DEBQ). Mean age was 61.2±9.7 years old (range 39-85 years). Physical assessment included height, weight, body mass index and obesity degree according World Health Organization. Statistical analyses were performed using SPSS 21.0. Means (SD), 95% confidence interval (CI) were calculated.Results. One hundred seventy-nine patients were classified as obese (range 30.0 – 53.9). Mean values for restraint, emotional and external eating for this obese group were 2.8±0.07 (95% CI 2.7-3.0), 3.3±0.08 (95% CI 3.2-3.5) and 3.0±0.05 (95% CI 2.9-3.2), respectively. Russian patients showed higher levels of external eating (p<0.0001) and emotional eating (p<.0001) than their UK counterparts, but levels of restraint eating did not differ by country (p=0.30). HbA1c was significantly lower in the Russian patients compared to the UK patients (p=0.04). Multiple regression analysis showed that emotional eating, but not restraint or external eating was a significant predictor of BMI even when controlling for age, sex, HbA1c and country (β = 0.56; p < 0.0001; 95%CI 1.03-3.0)Conclusion. Present study has shown that emotional eating is an important correlate of BMI in patients with T2DM patients. However, eating behaviour styles may differ by country.
A Simple and Practical Method for Rat Epididymal Sperm Count (Rattus norvegicus)
Authors: Luthfi Muhammad Ja’far
Published: October 2016

Sperm sample from epididymal source can be determined its number using minimal amount of equipment. These method will aid researcher and practitioner in sperm quality analysis to determined sperm number rapidly and practically.
Mathematical Modeling of Natural Gas Separation Using Hollow Fiber Membrane Modules by Application of Finite Element Method through Statistical Analysis
Authors: Dehkordi Javad Aminian , Hosseini Seyed Saeid , Kundu Prodip K. , Tan Nicolas R.
Published: October 2016

Hollow fiber membrane permeators used in the separation industry are proven as preferred modules representing various benefits and advantages to gas separation processes. In the present study, a mathematical model is proposed to predict the separation performance of natural gas using hollow fiber membrane modules. The model is used to perform sensitivity analysis to distinguish which process parameters influence the most and are necessary to be assessed appropriately. In this model, SRK equation was used to justify the nonideal behavior of gas mixtures and Joule-Thomson equation was employed to take into account the changes in the temperature due to permeation. Also, the changes in temperature along shell side was calculated via thermodynamic principles. In the proposed mathematical model, the temperature dependence of membrane permeance is justified by the Arrhenius-type equation. Furthermore, a surface mole fraction parameter is introduced to consider the effect of accumulation of less permeable component adjacent to the membrane surface in the feed side. The model is validated using experimental data. Central Composite Designs are used to gain response surface model. For this, fiber inner diameter, active fiber length, module diameter and number of fibers in the module are taken as the input variables related to the physical geometries. Results show that the number as well as the length of the fibers have the most influence on the membrane performance. The maximum mole fraction of CO2 in the permeate stream is observed for low number of fibers and fibers having smaller active lengths. Also results indicate that at constant active fiber length, increasing the number of fibers decreases the permeate mole fraction of CO2. The findings demonstrate the importance of considering appropriate physical geometries for designing hollow fiber membrane permeators for practical gas separation applications.
Modelling Study of Palladium Membrane Reactor Performance during Methan Steam Reforming using CFD Method
Authors: Ghasemzadeh Kamran , Andalib Ehsan , Basile Angelo
Published: October 2016

The main aim of this study is the investigation of dense palladium membrane reactor (MR) performance during methane steam reforming (MSR) reaction using computational fluid dynamic (CFD). To this purpose, a two-dimensional isothermal CFD model was developed and its validation was realized by comparing the theoretical results with our experimental data achieved in ITM of Italy. In this work, the CFD model was presented by COMSOL- Multiphysics software version 5. The reaction rate expressions and kinetics parameters were used from literatures. According to validation results, a good agreement between modeling results and experimental data was found. After model validation, the effect of the some important operating parameters (temperature and pressure) on the performance of palladium MR was studied in terms of methane conversion and hydrogen recovery. The CFD model presented velocity and pressure profiles in both side of MR and also molar fraction of different species in permeate and retentate streams. The modeling results showed that the palladium MR presents comparable performance with respect to traditional reactor (TR) in terms of the methane conversion, especially, at lower temperatures and higher pressures. In fact, CFD results indicated that palladium MR performance was improved by increasing the reaction pressure, while this parameter had negative effect on the TR performance. This result related to increasing the hydrogen permeance through the palladium membrane by enhancement of pressure gradient. Indeed, this shift effect can provide a higher methane conversion in lower temperatures in the palladium MR. In particular, 99% methane conversion and 43% hydrogen recovery was achieved at 500°C and 1.5 atm.
Investigation of Palladium Membrane Reactor Performance during Ethanol Steam Reforming using CFD Method
Authors: Ghasemzadeh K. , Zeynali R. , Ahmadnejad F. , Babalou A. A. , Basile A.
Published: October 2016

The main purpose of present study is the analysis of dense palladium membrane reactor (MR) performance during ethanol steam reforming (ESR) reaction using computational fluid dynamic (CFD). To this aim, a two-dimensional and isothermal model based on CFD method was developed and results validation was tested by our experimental data achieved in ITM-CNR of Italy. In this work, Pd-based MR modeling was performed by using COMSOL-MULTIPHYSICS software. Regarding to model validation results, a good agreement was found between CFD model results and experimental data. Moreover, in this study, the effects of the some important operating parameters (reaction temperature and pressure) on the performance of Pd-based MR was studied in terms of ethanol conversion and hydrogen recovery. Concerning to simulation results, the CFD model presented velocity and pressure profiles in both side of MR and also compositions of various species in permeate and retentate streams. The simulation results indicated that the Pd-based MR has better performance with respect to traditional reactor (TR) in terms of the ethanol conversion, especially, at lower reaction temperatures and higher reactions pressures. As a consequence, CFD model results illustrated that Pd-based MR performance was improved by increasing the reaction pressure, while this parameter had negative effect on the TR performance. This result related to enhancement of hydrogen permeance through the palladium membrane by increasing the pressure gradient. Indeed, this shift effect can provide a higher ethanol conversion in lower temperatures in the Pd-based MR. In particular, 98% ethanol conversion and 37% hydrogen recovery was achieved at 350°C and 2 atm.
The Effect of Module Geometry on Heat and Mass Transfer in Membrane Distillation
Authors: Ahadi Hossein , Karimi-Sabet Javad , Shariaty-Niassar Mojtaba
Published: October 2016

Some features of Direct Contact Membrane Distillation (DCMD), as one of the interesting membrane processes, has been studied in this effort. 3D computational fluid dynamic simulations were carried out to investigate some geometric parameter effects on flat sheet membrane module performance. It is obvious that using of baffles could noticeably improve the performance of the system. Hence, in present work, some baffle configurations were simulated and some parameters like temperature polarization, vapor flux and pressure drop through module length were investigated. The Simulation was performed based on neglecting viscous flow in membrane pores and dusty gas model was applied to predict vapor flux through membrane. Simulation results predicted that by using the new configuration we could have 40–60% vapor flux improvement (depend on inflow velocity) compared to a module without baffle. It was found that the average temperature polarization (TP), as a proper criteria, was higher for baffled one in all situations.
Designing Better Membrane Modules Using CFD
Authors: Haddadi Sisakht Bahram , Jordan Christian , Schretter Philipp , Lassmann Tino , Harasek Michael
Published: October 2016

In the last decades, a large number of studies have been carried out on the utilization of membranes in separation processes. However, most of these studies deal with material properties, experimental investigations and process modeling. Only quite a few authors utilized computational fluid dynamics (CFD) to analyze the flow and mass transfer in membrane modules. Using CFD it is possible to obtain spatially resolved information on the behavior of membrane modules, allowing for the investigation of geometric effects on the performance of the module. This includes e. g. the positioning of the permeate outlets, the flow alignment (co- and/or counter-current), the use of spacers and other mixing promoters and also the subject of concentration polarization close to the membrane surface. In our present study we made use of OpenFOAM®, which is a free open sourced CFD toolbox. The toolbox enables for introducing new solver code, membraneFoam, based on the standard multicomponent solver reactingFoam. In membraneFoam suitable source and sink terms have been added to account for trans-membrane flux – in this case based on the solution-diffusion model for glassy polymer gas permeation membranes. The solver has been preliminary validated using literature data obtained from a process simulation code. In a first stage of the research work the positioning of the permeate outlet and the flow alignment have been investigated for a hollow fiber gas permeation module. By adjusting the position of the permeate outlet the shell side flow can be co-current, counter-current or mixed type relative to the retentate flow inside the fibers. Since this influences the driving force for the trans-membrane flux, effects on the module performance are expected which have been analyzed using the described membraneFoam CFD approach.
Mechanistic insight from murine models of Netherton syndrome
Authors: Keuylian Zela , Hovnanian Alain
Published: October 2016

Protease regulation plays a crucial role in skin homeostasis and inflammation as revealed by the identification of loss-of-function mutations in SPINK5 (serine protease inhibitor of Kazal type 5) in Netherton sydrome (NS). SPINK5 encodes LEKTI (lympho-epithelial Kazal type related inhibitor), a multidomain serine protease inhibitor expressed in all stratified epithelia. Our laboratory has developed a number of murine models which have been instrumental in dissecting the pathogenesis of NS. This minireview discusses the major findings of these models and emphasizes the role of protease regulation, especially kallikrein-related peptidases in NS.
Photocatalytic Treatment of Binary Mixture of Dyes using UV/TiO2 Process: Calibration, Modeling, Optimization and Mineralization Study
Authors: Garg Alok , Sangal Vikas K. , Bajpai Pramod K.
Published: October 2016

Photocatalytic treatment of a binary dye mixture (Acid Blue 113 (AB113) and Acid Red 114 (AR114)) has been done in a slurry pond reactor using TiO2 as a photocatalyst with UV light irradiation (UV-C). Two different methods, namely multivariate calibration and first order derivative spectrophotometric were used to quantify each dye separately in binary dye solutions. The behavior of the photocatalytic degradation of a binary dye mixture was predicted using an artificial neural network (ANN) model. Five process parameters (initial concentration of AB113 dye, initial concentration of AR114 dye, TiO2 dose, initial pH of the dye mixture and time were used as inputs and decolorization efficiency of AB113 and AR114 were used as output of the ANN. The parametric optimization has been done by the multi-response optimization with desirability function methodology. Optimization by Central Composite Design (CCD) effectively handles the relations among optimizing process variables and its prediction concurred well with the experimental run and artificial neural network (ANN) model. The reaction kinetic rates of decolorization of both dyes (AB113 and AR114) were found to be first order. Total organic carbon (TOC) removal and possible reaction pathway show the total mineralization of both dyes in binary dye mixture.