Showing papers in "Endocrine Regulations in 2016"

Alternative renin-angiotensin system pathways in adipose tissue and their role in the pathogenesis of obesity.

Abstract: Adipose tissue expresses all the renin-angiotensin system (RAS) components that play an important role in the adipogenesis, lipid and glucose metabolism regulation in an auto/paracrine manner. The classical RAS has been found to be over-activated during the adipose tissue enlargement, thus elevated generation of angiotensin II (Ang II) may contribute to the obesity pathogenesis. The contemporary view on the RAS has become more complex with the discovery of alternative pathways, including angiotensin-converting enzyme 2 (ACE2)/angiotensin (Ang)-(1-7)/Mas receptor, (pro)renin receptor, as well as angiotensin IV(Ang IV)/AT4 receptor. Ang-(1-7) via Mas receptor counteracts with most of the deleterious effects of the Ang II-mediated by AT1 receptor implying its beneficial role in the glucose and lipid metabolism, oxidative stress, inflammation, and insulin resistance. Pro(renin) receptor may play a role (at least partial) in the pathogenesis of the obesity by increasing the local production of Ang II in adipose tissue as well as triggering signal transduction independently of Ang II. In this review, modulation of alternative RAS pathways in adipose tissue during obesity is discussed and the involvement of Ang-(1-7), (pro)renin and AT4 receptors in the regulation of adipose tissue homeostasis and insulin resistance is summarized.

Gestational diabetes: An overview with attention for developing countries.

Abstract: Gestational diabetes mellitus (GDM) is defined as a glucose intolerance that occurs for the first time or it is first identified during pregnancy. The GDM etiology is multifactorial. It has not completely been established yet and several known risk factors may contribute to its onset. To date, there are no shared guidelines on the management and follow-up, especially regarding the low-income countries. In this paper, we describe the state of art about epidemiology, physiopathology, diagnosis, and management of GDM. Moreover, we focus on the current state in low income countries trying to outline basis for further research.

Elevated neutrophil-lymphocyte ratio in patients with euthyroid chronic autoimmune thyreotidis

Abstract: OBJECTIVE The neutrophil-lymphocyte ratio (NLR), determined from peripheral blood, is accepted as an available and practical indicator of the systemic inflammation. In this study, we aimed to determine whether the NLR was higher in euthyroid chronic autoimmune thyreotidis (CAT) patients compared to a healthy control group. METHODS A total of 112 patients were enrolled in this study, including 59 patients with euthyroid CAT on any form of therapy and 53 healthy controls. Th e CAT patients were similar in age to the healthy control group (mean 33.9±12.8 years versus 30.2±12.4 years, p=0.10). Measurements were available for the white blood cells (WBC), neutrophils, lymphocytes, platelets, C-reactive protein (CRP), thyroid peroxidase immune antibody (anti-TPO), and anti-thyroglobulin immune antibody (anti-TG). The NLR and platelet-lymphocyte ratio (PLR) were calculated. Differences between the CAT and control groups were tested using the student's t-test and the correlations were determined using Pearson's correlation coefficients. RESULTS There were no differences between the CAT and control groups for WBCs (7.9±0.3 and 7.4±0.2, respectively; p=0.1) or neutrophils (5.5±0.3 and 5.4±1.1; p=0.9), but lymphocytes were higher in the CAT group (3.1±0.5 vs. 2.04±0.1; p=0.05) as was the NLR (4.0±0.7 vs. 2.0±0.1; p=0.01). Th e NLR was positively correlated with CRP (r=0.6, p<0.001), anti-TPO (r=0.3, p<0.001), anti-TG (r=0.3, p=0.006), WBCs (r=0.4, p<0.001), and the PLR (r=0.73, p<0.001). The PLR was also higher in the CAT than the control group (p=0.02). CONCLUSIONS In this study, we found that NLR values were higher in euthyroid CAT patients than in a healthy control group and that NLR correlated with autoantibodies used to diagnose the disease.

The role of retinoic acid receptors and their cognate ligands in reproduction in a context of triorganotin based endocrine disrupting chemicals

Abstract: Retinoic acid (RA), an active form of vitamin A, regulates the embryonic development, male and female reproduction and induces important effects on the cell development, proliferation, and differentiation. These effects are mediated by the retinoid (RAR) and rexinoid nuclear receptors (RXR), which are considered to be a ligand-activated, DNA-binding, trans-acting, and transcription-modulating proteins, involved in a general molecular mechanism responsible for the transcriptional responses in target genes. Organotin compounds are typical environmental contaminants and suspected endocrine disrupting substances. They may affect processes of reproductive system in mammals, predominantly via nuclear receptor signaling pathways. Triorganotins, such as tributyltin chloride (TBTCl) and triphenyltin chloride (TPTCl), are capable to bind to RXR molecules, and thus represent potent agonists of RXR subtypes of nuclear receptors not sharing any structural characteristics with endogenous ligands of nuclear receptors. Th is article summarizes selected effects of biologically active retinoids and rexinoids on both male and female reproduction and also deals with the effects of organotin compounds evoking endocrine disrupting actions in reproduction.

Continuous cold exposure induces an anti-inflammatory response in mesenteric adipose tissue associated with catecholamine production and thermogenin expression in rats.

Abstract: Objective Continuous exposure to cold leads to an activation of adaptive thermogenesis in the brown adipose tissue and induction of brown/beige cell phenotype in the white adipose tissue. Thermogenic response is associated with alternatively activated macrophages producing catecholamines, which subsequently activate the uncoupling protein 1 (UCP-1). The aim of this work was to elucidate the effect of cold exposure on catecholamine and immune responses associated with adipocyte browning in the mesenteric adipose tissue (mWAT) of rat. Methods The rats were exposed to continuous cold (4 °C) for 1 or 7 days. Catecholamines production and gene expressions of inflammatory and other factors, related to adipocyte "browning", were analyzed in the homogenized mWAT samples using 2-CAT ELISA kits. Results Cold exposure induced a sympathetic response in the mWAT, evidenced by the tyrosine hydroxylase (TH) protein level rise. Induction of non-sympathetical catecholamine production was observed 7 days after cold exposure by elevated TH and phenylethanolamine-N-methyltransferase (PNMT) expression, leading to an increased epinephrine levels. Cold exposure for 7 days stimulated the infiltration of macrophages, evaluated by F4/80 and CD68 expressions, and expression of anti-inflammatory mediators, while pro-inflammatory cytokines were inhibited. Anti- inflammatory response, accompanied by de novo catecholamine production and up-regulation of β3-adrenergic receptors, led to the stimulation of UCP-1 and PGC1α expression, suggesting a cold-induced "browning" of the mWAT, mediated by alternatively activated macrophages. Conclusions The present data indicate that prolonged cold exposure may induce anti-inflammatory response in mWAT associated with induction of UCP-1 expression. Although functional thermogenesis in the mWAT is most likely redundant, a highly efficient dissipation of energy by UCP1 may affect the energy homeostasis in this visceral fat.

Flaxseed oil supplementation manipulates correlations between serum individual mol % free fatty acid levels and insulin resistance in type 2 diabetics. Insulin resistance and percent remaining pancreatic β-cell function are unaffected.

Abstract: Objectives Elevated total serum free fatty acids (FFAs) concentrations have been suggested, controversially, to enhance insulin resistance and decrease percent remaining β-cell function. However, concentrations of individual serum FFAs have never been published in terms of their relationship (correlation) to homeostatic model assessment-insulin resistance (HOMA-IR) and percent remaining β-cell function (HOMA-%β) in the type 2 diabetics (T2Ds). Alpha-linolenic acid consumption has a negative correlation with the insulin resistance, which in turn is negatively correlated with the remaining β-cell function. The primary objective was to test the hypothesis that there would be different relationship (correlation) between the blood serum individual free FFA mol % levels and HOMA-IR and/or HOMA-%β in T2D. The secondary objective was to test the hypothesis that flaxseed oil, previously being shown to be ineffective in the glycemic control in T2Ds, may alter these correlations in a statistically significant manner as well as HOMA-IR and/or HOMA-%β. Methods Patients were recruited via a newspaper advertisement and two physicians have been employed. All the patients came to visit one and three months later for a second visit. At the second visit, the subjects were randomly assigned (double blind) to flaxseed or safflower oil treatment for three months, until the third visit. Results Different statistically significant correlations or trends towards among some serum individual free FFA mol % levels and HOMA-IR and HOMA-%β, pre- and post-flaxseed and safflower oil supplementation were found. However, flaxseed oil had no impact on HOMA-IR or HOMA-%β despite statistically significant alterations in correlations compared to baseline HOMA-IR. Conclusions The obtained data indicate that high doses of flaxseed oil have no statistically significant effect on HOMA-IR or HOMA-%β in T2Ds, probably due to the additive effects of negative and positive correlations.

Effect of hypoxia on the expression of genes encoding insulin-like growth factors and some related proteins in U87 glioma cells without IRE1 function

Abstract: Objective The aim of the present study was to investigate the effect of hypoxia on the expression of genes encoding insulin-like growth factors (IGF1 and IGF2), their receptor (IGF1R), binding protein-4 (IGFBP4), and stanniocalcin 2 (STC2) in U87 glioma cells in relation to inhibition of endoplasmic reticulum stress signaling mediated by IRE1 (inositol requiring enzyme 1) for evaluation of their possible significance in the control of tumor growth. Methods The expression of IGF1, IGF2, IGF1R, IGFBP4, and STC2 genes in U87 glioma cells transfected by empty vector pcDNA3.1 (control) and cells without IRE1 signaling enzyme function (transfected by dnIRE1) upon hypoxia was studied by qPCR. Results The expression of IGF1 and IGF2 genes is down-regulated in glioma cells without IRE1 signaling enzyme function in comparison with the control cells. At the same time, the expression of IGF1R, IGFBP4, and STC2 genes was up-regulated in glioma cells upon inhibition of IRE1, with more significant changes for IGFBP4 and STC2 genes. We also showed that hypoxia does not change significantly the expression of IGF1, IGF2, and IGF1R genes but up-regulated IGFBP4 and STC2 genes expression in control glioma cells. Moreover, the inhibition of both enzymatic activities (kinase and endoribonuclease) of IRE1 in glioma cells does not change significantly the effect of hypoxia on the expression of IGF1, IGF1R, and IGFBP4 genes but introduces sensitivity of IGF2 gene to hypoxic condition. Thus, the expression of IGF2 gene is resistant to hypoxia only in control glioma cells and significantly down-regulated in cells without functional activity of IRE1 signaling enzyme, which is central mediator of the unfolded protein response and an important component of the tumor growth as well as metabolic diseases. Conclusions Results of this study demonstrate that the expression of IGF1 and IGF1R genes is resistant to hypoxic condition both in control U87 glioma cells and cells without IRE1 signaling enzyme function. However, hypoxia significantly up-regulates the expression of IGFBP4 gene independently on the inhibition of IRE1 enzyme. These data show that proteins encoded by these genes are resistant to hypoxia except IGFBP4 and participate in the regulation of metabolic and proliferative processes through IRE1 signaling.

Protective effects of boron and vitamin E on ethylene glycol-induced renal crystal calcium deposition in rat

Abstract: OBJECTIVES Kidney stone disease is a common form of renal disease. Antioxidants, such as vitamin E (Vit E) and boron, are substances that reduce the damage caused by oxidation. METHODS Adult male rats were divided into 5 groups (n=6). In group 1, rats received standard food and water for 28 days (control group); in group 2, standard rodent food and water with 0.75% ethylene glycol/d (dissolved in drinking water) (EG Group); in group 3, similar to group 2, with 3 mg of boron/d (dissolved in water) (EG+B Group); in group 4, similar to group 2, with 200 IU of vitamin E injected intraperitoneally on the first day and the 14th day, (EG+Vit E Group); in group 5, mix of groups 3 and 4, respectively (EG+B+Vit E Group). RESULTS Kidney sections showed that crystals in the EG group increased significantly in comparison with the control group. Crystal calcium deposition score in groups of EG+B (160), EG+Vit E, and EG+B+Vit E showed a significant decrease compared to EG group. Measurement of the renal tubules area and renal tubular epithelial histological score showed the highest significant dilation in the EG group. Tubular dilation in the EG+B+Vit E group decreased compared to the EG+B and EG+Vit E groups. CONCLUSIONS Efficient effect of boron and Vit E supplements, separately and in combination, has a complimentary effect in protection against the formation of kidney stones, probably by decreasing oxidative stress.

Role of interlekin-35 as a biomarker in patients with newly diagnosed Hashimoto's thyroiditis.

Abstract: Objective Interleukin-35 (IL-35), an interleukin-12 (IL-12) cytokine family member, is shown to be a potent immunosuppressive and anti-inflammatory cytokine. Inducible regulatory T cells (Tregs) produce IL-35 that mediates the immune inhibitory function of Tregs. Growing evidence revealed that upregulation of IL-35 expression may play a critical role in the prevention of autoimmune diseases in various experimental autoimmunity models and vice versa. Hashimoto's thyroiditis (HT) is considered to be a Treg cell-related autoimmune disease with loss of self-tolerance. Methods One hundred-twenty eight subjects, newly diagnosed hypothyroid HT patients [56 overt (Group 1), 72 subclinical hypothyroid (Group 2)] and 38 healthy controls (Group 3) were enrolled in the study. The levels of serum IL-35 were determined by enzyme-linked immunosorbent assay (ELISA). Results Serum IL-35 levels were lower in the HT group when compared with subclinical HT group [304.5 (834.6) pg/ml vs. 636.1 (1542.0) pg/ml, p=0.004] and control cases [304.5 (834.6) pg/ml vs. 1064.7 (2526.8) pg/ml, p Conclusion The results suggest that IL-35 may play a role in the pathogenesis of HT.

Inhibition of IRE1 signaling affects the expression of genes encoded glucocorticoid receptor and some related factors and their hypoxic regulation in U87 glioma cells.

Abstract: OBJECTIVE The aim of the present investigation was to examine the effect of inhibition of endoplasmic reticulum stress signaling, mediated by IRE1 (inositol requiring enzyme 1), which is a central mediator of the unfolded protein response on the expression of genes encoding glucocorticoid receptor (NR3C1) and some related proteins (SGK1, SGK3, NCOA1, NCOA2, ARHGAP35, NNT) and their hypoxic regulation in U87 glioma cells for evaluation of their possible significance in the control of the glioma growth. METHODS The expression of NR3C1,SGK1,SGK3, NCOA1, NCOA2, ARHGAP35, and NNT genes in U87 glioma cells, transfected by empty vector pcDNA3.1 (control) and cells without IRE1 signaling enzyme function (transfected by dnIRE1) upon hypoxia, was studied by quantitative polymerase chain reaction. RESULTS Inhibition of IRE1 signaling enzyme function up-regulates the expression of NR3C1, SGK1, NCOA1, NCOA2, ARHGAP35, and NNT genes in U87 glioma cells in comparison with the control glioma cells, with more significant changes for NR3C1, SGK1, and NNT genes. At the same time, the expression of SGK3 gene is strongly down-regulated in glioma cells upon inhibition of IRE1. We have also shown that hypoxia increases the expression of NR3C1, SGK1, NCOA2, ARHGAP35, and NNT genes but decreases SGK3 and NCOA1 genes expression in control glioma cells. Moreover, the inhibition of both enzymatic activities (kinase and endoribonuclease) of IRE1 in U87 glioma cells enhances the eff ect of hypoxia on the expression of SGK1, SGK3, and NNT genes, but decreases the sensitivity of NR3C1 gene to hypoxic condition. Furthermore, the expression of NCOA1 gene is resistant to hypoxia in control glioma cells, but NCOA2 and ARHGAP35 genes are resistant to this condition in glioma cells without functional activity of IRE1 signaling enzyme. CONCLUSIONS Results of this investigation demonstrate that inhibition of IRE1 signaling enzyme function affects the expression of NR3C1, SGK1, SGK3, NCOA1, NCOA2, ARHGAP35, and NNT genes in U87 glioma cells in gene specific manner and that all these genes are regulated by hypoxia preferentially through IRE1 signaling pathway of the endoplasmic reticulum stress.

Pancrelipase treatment in a patient with the history of Roux-en-Y gastric bypass operation that developed resistant hypocalcemia secondary to total thyroidectomy.

Abstract: Objective Roux-en-Y gastric bypass (RYGB) is an independent risk factor for moderate hypocalcaemia and may lead to the development of resistant hypocalcaemia following thyroid surgery. Subject and Results. A 35-year old female patient was referred to our hospital by her family physician for treatment of resistant hypocalcaemia. The patient underwent RYGB three years ago and a total thyroidectomy for a benign thyroid nodule one year ago. Calcitriol, calcium carbonate, magnesium oxide, and ergocalciferol therapeutic dosages were incremented. Despite dosage increments, the desired calcium levels were not achieved. In the sixth month after admission to our hospital, pancrelipase was added to patient's treatment scheme. On the following visit, a good calcium increase had been achieved. Conclusion This report presents a case history of RYGB and resistant hypocalcaemia, which developed after thyroid surgery and positively responded to pancrelipase treatment.

Mechanisms involved in the regulation of neuropeptide-mediated neurite outgrowth: a minireview.

Abstract: The present knowledge, regarding the neuronal growth and neurite extension, includes neuropeptide action in the central nervous system. Research reports have brought much information about the multiple intracellular signaling pathways of neuropeptides. However, regardless of the differences in the local responses elicited by neuropeptides, there exist certain functional similarities in the effects of neuropeptides, mediated by their receptors. In the present review, data of the relevant studies, focused on G protein-coupled receptors activated by neuropeptides, are summarized. Particularly, receptors that activate phosphatidylinositol-calcium system and protein kinase C pathways, resulting in the reorganization of the neuronal cytoskeleton and changes in the neuronal morphology, are discussed. Based on our data received, we are showing that oxytocin increases the gene expression of GTPase cell division cycle protein 42 (Cdc42), implicated in many aspects of the neuronal growth and morphology. We are also paying a special attention to neurite extension and retraction in the context of neuropeptide regulation.

The prepulse inhibition deficit appearance is largely independent on the circadian cycle, body weight, and the gender of vasopressin deficient Brattleboro rat.

Abstract: OBJECTIVE A disturbance of sensorimotor gating measured by prepulse inhibition of acoustic startle (PPI) is one of the best tests of the schizophrenia-like behavior. Vasopressin was implicated in the development of schizophrenia; therefore, the naturally occurring vasopressin-deficient Brattleboro rat has been suggested to be a reliable non-pharmacological animal model. However, previous studies focusing on PPI deficit did not use proper control and despite clear gender differences in the development of the disorder, the effect of gender has been mostly neglected. METHODS First, we compared the "noise" and "tone" type prepulse at 73-77-81 dB intensity during the light or dark phase using small (~150 g) or big (~500 g) Wistar rats. The test parameters were validated by a pharmacological schizophrenia model (30 mg/kg ketamine i.p.). Than male, female, and lactating vasopressin-deficient animals were compared with +/+ ones. RESULTS We established that the prepulse "noise" type is not optimal for PPI testing. The cycle of the day as well as the body weight had no effect on PPI. Even if we compared vasopressin-deficient animals with their closely related +/+ controls, the PPI deficiency was visible with more pronounced effect at 77 dB prepulse intensity similarly to pharmacological schizophrenia model. Despite our expectation, the gender as well as lactation had no effect on the vasopressin-deficiency induced PPI deficit. CONCLUSIONS The present data confirmed and extended our previous studies that vasopressin-deficient rat is a good model of schizophrenia. It seems that female as well as lactating Brattleboro rats are useful tools for testing putative novel antipsychotics in line with special attention required for schizophrenic women.

Effect of the autonomic nervous system on cancer progression depends on the type of tumor: solid are more affected then ascitic tumors

Abstract: Objectives A number of recently published studies have shown that the sympathetic nervous system may influence cancer progression. There are, however, some ambiguities about the role of the parasympathetic nerves in the modulation of growth of different tumor types. Moreover, tumor models used for investigation of the autonomic neurotransmission role in the processes related to the cancer growth and progression are mainly of the solid nature. The knowledge about the nervous system involvement in the modulation of the development and progression of malignant ascites is only fragmental. Therefore, the aim of the present article was to summarize the results of our experimental studies focused on the elucidation of the role of the autonomic nervous system in the modulation of tumor growth in animals. We are summarizing data from studies, in which not only different experimental approaches in order to influence the autonomic neurotransmission, but also different tumor models have been used. Methods Three different types of tumor models, namely solid rat intra-abdominal fibrosarcoma, solid murine subcutaneous melanoma, and rat ascites hepatoma, and three types of interventions have been used in order to modulate the autonomic neurotransmission, specifically chemical sympathectomy, subdiaphragmatic vagotomy, or the electric stimulation of the vagus nerve. Results We have proved a strong stimulatory effect of the sympathetic nerves on the development and growth in both solid tumors, rat fibrosarcoma as well as murine melanoma, and significant inhibitory impact on the survival time of tumor-bearing animals. The progression of ascites hepatoma in rats was not influenced by chemical sympathectomy. Modulation of parasympathetic signalization by vagotomy or vagal nerve stimulation does not affect fibrosarcoma and ascites hepatoma growth and survival of the tumor-bearing rats. Conclusions Based on the obtained data, it seems that the solid types of tumors are suitable substrate for the direct action of neurotransmitters released especially from the sympathetic nerves. In contrast, it appears that the malignant ascites are not under the direct autonomic nerves control; however, an indirect action via the immune functions modulation cannot be excluded.

Micro RNAs: an arguable appraisal in medicine.

Abstract: Micro RNAs (miRNAs) represent a newly discovered class of regulatory molecules in the human body. miRNA is a short double stranded RNA sequence interfering with mRNA, causing in most cases, inhibition of translation. Synthesis of miRNAs shows an increasing developmental pattern and postnatally miRNAs are synthesized in all cells possessing transcriptional machinery. miRNAs usually target several mRNAs and therefore conclusive evidences proving their functions are not always ease to be acquired. In spite of this difficulty, functions of miRNAs were firmly established in the development, the cardiovascular and neural diseases, and cancer. Many miRNAs have been reported to be associated with physiological state of cells and/or tissues. This finding becomes fundamental, especially when consider that these miRNAs can be released from cell into intracellular space or circulation. Correlation between miRNA production in tissues and its contribution to multisource miRNA pool in the circulation is in a focus of biomarker-oriented researchers. Recently, circulating miRNAs have been suggested to be applicable as biomarkers in several types of cancer, cardiovascular injury, and diabetes. Role of miRNAs in the organism intercellular signaling is still under the broad investigation. Several miRNA mimics, intended for treatment of disease, are being currently tested in the clinical trials.

Progress in micro RNA focused research in endocrinology

Abstract: Micro RNAs (miRNAs) are small regulatory molecules of increasing biologists' interest miRNAs, unlikely mRNA, do not encode proteins It is a class of small double stranded RNA molecules that via their seed sequence interact with mRNA and inhibit its expression It has been estimated that 30% of human gene expression is regulated by miRNAs One miRNA usually targets several mRNAs and one mRNA can be regulated by several miRNAs miRNA biogenesis is realized by key enzymes, Drosha and Dicer miRNA/mRNA interaction depends on binding to RNA-induced silencing complex Today, complete commercially available methodical proposals for miRNA investigation are available There are techniques allowing the identification of new miRNAs and new miRNA targets, validation of predicted targets, measurement of miRNAs and their precursor levels, and validation of physiological role of miRNAs under in vitro and in vivo conditions miRNAs have been shown to influence gene expression in several endocrine glands, including pancreas, ovary, testes, hypothalamus, and pituitary

Sympathectomized tumor-bearing mice survive longer but develop bigger melanomas.

Abstract: Objectives Previously we have shown that 20 days after the tumor cells injection smaller melanomas have been developed in chemically sympathectomized mice in comparison with animals having intact sympathetic nervous system. However, it is known that chemical sympathectomy reduces the sympathetic neurotransmission only temporarily. In the present study, we monitored the survival of the sympathectomized mice with melanoma with an attempt to find out how long the suppressing effect of sympathectomy on the melanoma growth may endure. Methods The chemical sympathectomy was performed by intraperitoneal injection of neurotoxin 6-hydroxydopamine in male C57BL/6J mice. Seven days later, the animals were injected subcutaneously with B16-F10 melanoma cells. Then, melanoma development, survival of the tumor-bearing mice and weight of the developed tumor mass were analyzed. Results Sympathectomy delayed the development of the palpable tumors (18th day vs.14th day) and significantly prolonged the survival of the tumor-bearing mice (median 34 days vs. 29 days). However, the weight of the developed melanoma was significantly increased in the sympathectomized mice in comparison with the animals having intact sympathetic nervous system. Conclusions The data of the present study showed that effect of the chemical sympathectomy, performed before the tumor growth induction, persisted even at the time when sympathetic nerves started to regenerate that resulted in a prolonged survival of the mice with melanoma. However, comparing to our previous study, in which we have shown a reduced tumor mass in earlier stages of the tumor growth, specifically 20 days after melanoma cells injection, now we indicate that in later stages of the melanoma progression, the tumor mass was significantly increased in sympathectomized animals. These contra-intuitive findings may indicate that interventions affecting the sympathetic nervous system may exert complex effect on the tumor progression. Based on these data we may suggest that the potential therapeutic interventions affecting the sympathetic signaling in the tumor tissue and its microenvironment should attenuate the sympathetic neurotransmission not only temporarily but till the complete regression of the tumor tissue.

Newly diagnosed primary hypothyroidism applicant with massive pericardial effusion and acute renal failure.

Abstract: Objective While non-symptomatic pericardial effusion is seen in primary hypothyroidism, massive pericardial effusion is a very rare finding. In the literature, newly diagnosed primary hypothyroidism cases presenting with massive pericardial effusion or acute renal failure are present, but we did not encounter any case first presenting with combination of two signs. In this case report, primary hypothyroidism case that presenting with massive pericardial effusion and acute renal failure will be discussed. Subject and Results. Forty-eight years old male patient was hospitalized with shortness of breath, chest pain, swelling of the eyelids and bilateral limbs complaints. On chest radiograph heart shadow was deleted, pleural effusion was present until the middle zone of the left lung. Biochemical parameters (urea, creatinine, alanine aminotransferase aspartate aminotransferase, lactate dehydrogenase, sodium, potassium, creatine kinase, Troponin I, CK-MB, erythrocyte sedimentation rate, c-reactive protein) and thyroid stimulating hormone (TSH, 52.6 μg/ml), free triiodothyronine (T3, 0.61pg/ml), free thyroxine (T4, 0.12 ng/dl), anti thyroperoxydase (343 IU/ml), anti thyroglobulin (1604 IU/ml), were analyzed. The patient underwent pericardiocentesis. Levothyroxine treatment started with a dose of 0.05 mg per day and increased gradually until the optimum dose provided. At the end of the third month, the values of TSH, free T4, and free T3 were measured (2.3 μg/ml, 1.1 ng/dl, 2.54 pg/ml, respectively). The patient recovered completely and pericardial effusion was not detected in echocardiography. Conclusion Massive PE and acute renal failure due to primary hypothyroidism is a rare clinical condition. Primary hypothyroidism should be kept in mind in patients with symptoms like shortness of breath, chest pain, and generalized edema; moreover, when acute renal failure and PE were detected. It should be considered that patient's biochemical parameters can improve starting from the two weeks after levothyroxine treatment started with pericardiocentesis in severe symptomatic patients.

Handedness and gender influence blood pressure in young healthy men and women: A pilot study.

Abstract: OBJECTIVE The type and level of sex steroids influence blood pressure (BP). It has been suggested that functional brain asymmetries may be influenced by sex hormones. In addition, there are inter-arm differences in BP not yet related with handedness. In this study, we hypothesize a possible association between sex hormones, handedness, and inter-arm differences in blood pressure. METHODS To analyze this hypothesis, we measured BP in the left and right arm of the left and right handed adult young men and women in menstrual and ovulatory phase and calculated their mean arterial pressure (MAP). RESULTS Significant differences depending on sex, arm, handedness or phase of the cycle were observed. MAP was mostly higher in men than in women. Remarkably, in women, the highest levels were observed in the left handed in menstrual phase. Interestingly, the level of handedness correlated negatively with MAP measured in the left arm of right-handed women in the ovulatory phase but positively with the MAP measured in the right arm of right-handed women in the menstrual phase. CONCLUSIONS These results may reflect an asymmetrical modulatory influence of sex hormones in BP control.

Multiple functions and essential roles of nuclear receptor coactivators of bHLH-PAS family.

Abstract: Classical non-peptide hormones, such as steroids, retinoids, thyroid hormones, vitamin D3 and their derivatives including prostaglandins, benzoates, oxysterols, and bile acids, are collectively designated as small lipophilic ligands, acting via binding to the nuclear receptors (NRs). The NRs form a large superfamily of transcription factors that participate virtually in every key biological process. They control various aspects of animal development, fertility, gametogenesis, and numerous metabolic pathways, and can be misregulated in many types of cancers. Their enormous functional plasticity, as transcription factors, relates in part to NR-mediated interactions with plethora of coregulatory proteins upon ligand binding to their ligand binding domains (LBD), or following covalent modification. Here, we review some general views of a specific group of NR coregulators, so-called nuclear receptor coactivators (NRCs) or steroid receptor coactivators (SRCs) and highlight some of their unique functions/roles, which are less extensively mentioned and discussed in other reviews. We also try to pinpoint few neglected moments in the cooperative action of SRCs, which may also indicate their variable roles in the hormone-independent signaling pathways.

Comparison of clinical and biochemical variables in type 2 diabetes mellitus patients and their first-degree relatives with metabolic syndrome in Benin City, Nigeria: A cross sectional case controlled study.

Abstract: Objective Type 2 diabetes mellitus (T2DM) is characterized by a relative insulin deficiency or insulin resistance. It is also associated with a cluster of metabolic abnormalities, including hyper-tension and dyslipidemia. Although there are many studies that have studied the metabolic abnormalities in T2DM patients with metabolic syndrome (MetS), only few of them have assessed the metabolic abnormalities in their first-degree relatives (FDRs) who had MetS. The aim of this study is to compare the clinical and biochemical variables in T2DM subjects and their FDRs without diabetes in Benin City, Nigeria. Methods This is a cross sectional case control study including 124 T2DM patients, 96 FDR of T2DM subjects, and 96 controls recruited using convenience sampling. Data were collected using a questionnaire-administered technique. Variables of interest that were assessed included anthropometric indices like waist circumference (WC), hip circumference (HC), waist:hip ratio (WHR), body mass index (BMI), systolic blood pressure (SBP), diastolic blood pressure (DBP), serum lipid profile, fasting plasma glucose (FPG), hemoglobin A1c (HbA1c), proteinuria, and microalbuminuria. The 1999 World Health Organization (WHO) criteria were used to make a diagnosis of metabolic syndrome. The Chi-square test was used for comparison of proportions. P-value of less than 0.05 was taken as statistically significant. The student t-test was used to compare means and test for significant differences in the anthropometric and the metabolic indices. Results The prevalence of the MetS in T2DM persons was 87.1%, 16.7% in the FDR group, and 13.5% in the control group according to the WHO criteria. The mean value of HbA1c was significantly higher in T2DM subjects with MetS (p 0.05). The mean values of WHR, BMI, SBP, DBP, and triglyceride were higher in persons with the MetS in the FDR group than in persons with the MetS in the T2DM group. The difference in the BMI and SBP was significant (p Conclusion The prevalence of MetS in subjects with T2DM in Nigeria is very high. Though, all the biochemical and clinical indices were higher in T2DM subjects with MetS, the mean HbA1c, BMI, and SBP was significantly higher when compared to their FDR who also have MetS.

An unusual case in endocrinology practice: Suture granuloma

Abstract: Objective Suture granuloma, the rare complication of thyroidectomy, results from the use of nonabsorbable suture materials. Despite its typical ultrasound images and benign course, it carries utmost importance in the diff erential diagnosis of lymph nodes, recurrent nodules, and recurrence in the case of thyroid cancers. Subject and Results. Fifty four years old female patient, who underwent bilateral thyroidectomy in July 2010, was diagnosed with multinodular goiter and incidentally discovered micropapillary carcinoma (2 mm). Four years later, she was readmitted to hospital due to painless swelling in the right and left anterior neck region. Ultrasonography revealed nodules with irregular boundaries, containing micro- and macro-calcifications and hyperechoic lines in both sides of the thyroid bed and isthmus. Fine needle aspiration biopsy was performed in the right and left sided mass and the cytological examination was compatible with the diagnosis of the suture granuloma. Conclusions Suture granuloma should be considered in the differential diagnosis of the local recurrence.

Current status of iodine deficiency-related disorders prophylaxis in Slovakia - the life's work of Julian Podoba remained unfinished.

Abstract: OBJECTIVE Prophylaxis of iodine deficiency-related disorders with iodized salt in Slovakia was introduced in 1951. This prophylactic measure yielded remarkably good results. Endemic goiter and endemic cretinism disappeared. Sufficient iodine intake, mainly in children and adolescents, was confirmed in several local and international studies carried out in the period 1991-95. Unfortunately, since seventies, there has been no institution which would have dealt with iodine prophylaxis in such an extent as this important measure of Slovak preventive medicine would require. Neither systematic monitoring of iodine intake nor systematic population epidemiological studies have been carried out. We do not have any data on the iodine intake in pregnant women, the most vulnerable population group in relation to the iodine deficiency. During the period June 2014 - October 2015, we examined iodine excretion in 426 probands from three regions of Slovakia with an emphasis on the pregnant women. RESULTS Iodine intake was found to be sufficient, even more than adequate, in all age groups of Slovak population. The only population group with iodine intake borderline or very mild iodine deficiency are pregnant women. CONCLUSIONS 1/ Iodine nutrition in Slovakia is generally sufficient, even oversteps the requirement, with the exception of pregnant women. Iodine intake in pregnant women should be fortified by iodine containing multivitamin preparations. 2/ We recommend to include the examination of urinary iodine into the screening of thyropathies in early pregnancy. 3/ It is not enough to implement the iodine deficiency-related disorders prevention programs, it is also necessary to stabilize such programs over time and balance the benefits with possible side effects of this program.

A case of hypercalcaemic crisis secondary to coexistence of primary hyperparathyroidism and Graves' disease.

Abstract: A 46 year-old female patient presented to the hospital with ongoing and progressively increasing fatigue, severe nausea and vomiting, loss of appetite, constipation, palpitations and somnolence. Laboratory evaluation revealed a severe hypercalcaemia and overt hyperthyroidism. She was diagnosed with primary hyperparathyroidism accompanied by Graves' disease. The patient underwent total thyroidectomy and right inferior parathyroid gland adenoma excision on the 24th day of her admission to the hospital after calcium levels and free thyroid hormone levels were brought to normal ranges. We suggest that a possibility of simultaneous thyrotoxicosis and primary hyperparathyroidism in cases presenting with a hypercalcaemic crisis should be considered.