A Perspective on the Current Medical Approach of Advanced Medullary Thyroid Carcinoma

Medullary thyroid carcinoma (MTC) is a neuroendocrine tumor (NET), which originates in neural crest-derived calcitonin-producing C-cells. It occurs either sporadically or as a result of a germline mutation in the RET proto-oncogene, as in multiple endocrine neoplasia (MEN) syndrome type 2A including its variant familial MTC (FMTC) and type 2B. Currently, the only curative treatment for MTC is surgery, accompanied by lymph node dissection. However, the outcome is largely dependent on disease staging, with lymph node and distant metastases often identified at diagnosis, particularly in sporadic forms. Furthermore, the presence of cervical lymph node invasion at surgery predicts residual disease. The development of new treatments is strongly motivated by: (a) the low surgical cure rate when cervical lymph node metastases are present at the time of initial surgery, with 90% of patients having residual disease, (b) the high prevalence of distant metastases at initial diagnosis (lungs, bones and liver) and (c) the poor outcome in patients receiving cytotoxic chemotherapeutic agents. Herein, we focus on current nonsurgical options and perspectives in the treatment of MTC with emphasis on last year’s FDA-approved tyrosine kinase inhibitors (TKIs) and other systemic therapies that need to be considered in the setting of advanced disease

Metabolomics—A Promising Approach to Pituitary Adenomas

Background: Metabolomics—the novel science that evaluates the multitude of low-molecular-weight metabolites in a biological system, provides new data on pathogenic mechanisms of diseases, including endocrine tumors. Although development of metabolomic profiling in pituitary disorders is at an early stage, it seems to be a promising approach in the near future in identifying specific disease biomarkers and understanding cellular signaling networks.Objectives: To review the metabolomic profile and the contributions of metabolomics in pituitary adenomas (PA).Methods: A systematic review was conducted via PubMed, Web of Science Core Collection and Scopus databases, summarizing studies that have described metabolomic aspects of PA.Results: Liquid chromatography tandem mass spectrometry (LC-MS/MS) and nuclear magnetic resonance (NMR) spectrometry, which are traditional techniques employed in metabolomics, suggest amino acids metabolism appears to be primarily altered in PA. N-acetyl aspartate, choline-containing compounds and creatine appear as highly effective in differentiating PA from healthy tissue. Deoxycholic and 4-pyridoxic acids, 3-methyladipate, short chain fatty acids and glucose-6-phosphate unveil metabolite biomarkers in patients with Cushing's disease. Phosphoethanolamine, N-acetyl aspartate and myo-inositol are down regulated in prolactinoma, whereas aspartate, glutamate and glutamine are up regulated. Phosphoethanolamine, taurine, alanine, choline-containing compounds, homocysteine, and methionine were up regulated in unclassified PA across studies. Intraoperative use of ultra high mass resolution matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI-MSI), which allows localization and delineation between functional PA and healthy pituitary tissue, may contribute to achievement of complete tumor resection in addition to preservation of pituitary cell lines and vasopressin secretory cells, thus avoiding postoperative diabetes insipidus.Conclusion: Implementation of ultra high performance metabolomics analysis techniques in the study of PA will significantly improve diagnosis and, potentially, the therapeutic approach, by identifying highly specific disease biomarkers in addition to novel molecular pathogenic mechanisms. Ultra high mass resolution MALDI-MSI emerges as a helpful clinical tool in the neurosurgical treatment of pituitary tumors. Therefore, metabolomics appears to be a science with a promising prospect in the sphere of PA, and a starting point in pituitary care

The Role of Soluble α-klotho Protein in Acromegaly

Soluble α-klotho (sαKl) is an isoform of the α-klotho protein that regulates calcium metabolism but also has anti-aging, anti-apoptotic, and tumor suppressor effects. The assumption that sαKl could inhibit the insulin-like growth factor 1 (IGF-1) signaling pathway has increased the interest of its research in acromegaly - a pathology characterized by an excess of growth hormone (GH) and IGF-1. This review aimed to identify the role of sαKl in acromegaly. Most studies have identified higher concentrations of sαKl in acromegaly versus non-GH pituitary adenomas (PAs) or healthy subjects. Also, the sαKl level was higher in active acromegaly versus controlled or cured disease. Moreover, sαKl positively correlated with GH, IGF-1, and GH-secreting PA size. The increased level of sαKl seems to be due to the autonomous secretion of GH, considering their drastic decrease after transsphenoidal surgery. The data regarding the relationship between sαKl, age, and gender in acromegaly are inconsistent. The latest research noted a correlation between sαKl and various parameters for monitoring the quality of life in acromegaly. In conclusion, sαKl could reflect the disease activity. Furthermore, sαKl would represent an alternative for monitoring acromegalic patients with discrepancies between IGF-1 and GH

Degenerated Hopf bifurcation in the Fitzhugh-Nagumo system. 2. Bautin bifurcation

The results on the Hopf bifurcation obtained in [1] are completed with those concerning the degenerated Hopf bifurcation of Bautin type. They are deduced by normal forms technique and concern a biodynamical system related with Van der Pol oscillator. Numerical investigations carried out by methods from [2] are also reported

RESEARCHES CONCERNING CONTROLLING OF THE MAIZE LEAF WEEVIL (TANYMECUS DILATICOLLIS GYLL) IN LABORATORY CONDITIONS, USING HIGH PEST PRESSURE, AT NARDI FUNDULEA

Maize leaf weevil (Tanymecus dilaticollis) is main pest of the maize crops in south and south-east of Romania. Every year there were attacked approximate one million of hectares cultivated with maize, with different attack intensity degrees. In many cases pest attack is high, as result maize plants were destroyed and farmers must sow again. The attack is dangerous when plants are in first vegetation stages (BBCH 10-14). In this paper, there were presented results of insecticides testing, used for maize seeds treatment against T. dilaticollis attack, in laboratory conditions, using high pest pressure (4 insects/plant). It has used imidacloprid, clothianidin and thiamethoxam active ingredients from neonicotinoid insecticides class. Maize plants were sowed in plastic pots and insects were added in pots, after plants emergence (BBCH 10). It has recorded daily weevils mortality until 8 days from the starting of the experiment. Also it has recorded attack intensity of the weevils at maize plants, using a scale from 1 (plants not attacked) to 9 (total damages). In laboratory conditions, in case of high pest pressure, at control (untreated) variant the attack intensity of T. dilaticollis weevils at maize plants, on a scale from 1 to 9 was 8.63. At the end of the experiment, all plants from untreated variant were destroyed. In case of seeds treated with imidacloprid, clothianidin or thiamethoxam active ingredients pest attack ranged from 4.58 to 4.65. At these variants, weevils mortality ranged from 67.50 to 71.25 %. All maize plants from treated variants survive of the attack

Speed factors computed for pumping schedules in Water Distribution Networks: DDA versus PDA formulations

This paper focuses on a methodology allowing to derive the pumping schedule in Water Distribution Networks (WDN), upon a time dependent water demand. The selected test case is a previously studied WDN. Two pumping algorithms give different pumping rules. By solving the nonlinear system of equations, consisting of energy balance equations, mass balance equations and pumping rules, one gets the pumps speed factors. Solutions attached to the Pressure Driven Analysis (PDA) correspond to energy and cost savings, with respect to the solutions given by the Demand Driven Analysis (DDA). The methodology described in this paper is simple and rapid, but the iterative numerical method used to solve the system of equations is highly dependent on the starting guess