E-cadherin expression is associated with somatostatin analogue response in acromegaly

Acromegaly is a rare disease resulting from hypersecretion of growth hormone (GH) and insulin‐like growth factor 1 (IGF1) typically caused by pituitary adenomas, which is associated with increased mortality and morbidity. Somatostatin analogues (SSAs) represent the primary medical therapy for acromegaly and are currently used as first‐line treatment or as second‐line therapy after unsuccessful pituitary surgery. However, a considerable proportion of patients do not adequately respond to SSAs treatment, and therefore, there is an urgent need to identify biomarkers predictors of response to SSAs. The aim of this study was to examine E‐cadherin expression by immunohistochemistry in fifty‐five GH‐producing pituitary tumours and determine the potential association with response to SSAs as well as other clinical and histopathological features. Acromegaly patients with tumours expressing low E‐cadherin levels exhibit a worse response to SSAs. E‐cadherin levels are associated with GH‐producing tumour histological subtypes. Our results indicate that the immunohistochemical detection of E‐cadherin might be useful in categorizing acromegaly patients based on the response to SSAs.ISCIII‐Subdirección General de Evaluación y Fomento de la Investigación PI13/02043 PI16/00175FEDER PI13/02043 PI16/00175Junta de Andalucía A‐0023‐2015 A‐0003‐2016 CTS‐1406 BIO‐0139Andalusian Ministry of Health C‐0015‐2014CIBERobn PI13/ 02043 PI16/0017

Neurocognitive Function in Acromegaly after Surgical Resection of GH-Secreting Adenoma versus Naïve Acromegaly

Patients with active untreated acromegaly show mild to moderate neurocognitive disorders that are associated to chronic exposure to growth hormone (GH) and insulin-like growth factor (IGF-I) hypersecretion. However, it is unknown whether these disorders improve after controlling GH/IGF-I hypersecretion. The aim of this study was to compare neurocognitive functions of patients who successfully underwent GH-secreting adenoma transsphenoidal surgery (cured patients) with patients with naive acromegaly. In addition, we wanted to determine the impact of different clinical and biochemical variables on neurocognitive status in patients with active disease and after long-term cure. A battery of six standardized neuropsychological tests assessed attention, memory and executive functioning. In addition, a quantitative electroencephalography with Low-Resolution Electromagnetic Tomography (LORETA) solution was performed to obtain information about the neurophysiological state of the patients. Neurocognitive data was compared to that of a healthy control group. Multiple linear regression analysis was also conducted using clinical and hormonal parameters to obtain a set of independent predictors of neurocognitive state before and after cure. Both groups of patients scored significantly poorer than the healthy controls on memory tests, especially those assessing visual and verbal recall. Patients with cured acromegaly did not obtain better cognitive measures than naïve patients. Furthermore memory deficits were associated with decreased beta activity in left medial temporal cortex in both groups of patients. Regression analysis showed longer duration of untreated acromegaly was associated with more severe neurocognitive complications, regardless of the diagnostic group, whereas GH levels at the time of assessment was related to neurocognitive outcome only in naïve patients. Longer duration of post-operative biochemical remission of acromegaly was associated with better neurocognitive state. Overall, this data suggests that the effects of chronic exposure to GH/IGF-I hypersecretion could have long-term effects on brain functions. © 2013 Martín-Rodríguez et al.Funding for this project was provided by an R&D grant from Novartis Oncology and the Plan Andaluz de Investigación (CTS-444). DAC was supported by the “Ramón y Cajal” program (RYC-2006-001071) of the Spanish Ministry of Science and Innovation.Peer Reviewe

Relatório de estágio em farmácia comunitária

Relatório de estágio realizado no âmbito do Mestrado Integrado em Ciências Farmacêuticas, apresentado à Faculdade de Farmácia da Universidade de Coimbr

Application of Finite-State Transducers to the Acquisition of Verb Subcategorization Information

This paper presents the design and implementation of a finite-state syntactic grammar of Basque that has been used with the objective of extracting information about verb subcategorization instances from newspaper texts. After a partial parser has built basic syntactic units such as noun phrases, prepositional phrases, and sentential complements, a finite-state parser performs syntactic disambiguation, determination of clause boundaries and filtering of the results, in order to obtain a verb occurrence together with its associated syntactic components, either complements or adjuncts. The set of occurrences for each verb is then filtered by statistical measures that distinguish arguments from adjuncts

DESA1002 'Nine Quarter City' - <William Chan>

This semester has been an architectural journey to Venice. I have created a building that fits with the environment of Venice. As the city is build upon water, my program was based upon this important element. My project involved the combination of three programs: research centre, science centre and spectator seating. My concept for my building was based on the idea to make better use of circulation space. Instead of having space just to get to programmatic space, this circulation space also contained something of interest. For example, the escalators are also a gallery and the lifts also serve as an aquarium. I also experimented in my structure and cladding. The structural members were placed randomly, just like nature and the cladding was casted out of PVA glue to represent water. This was extremely challenging for me as it was difficult to work with the glue and the material when it dried. The cladding became white, stiffer and harder to work with. Throughout these exercises I have been able to develop my own conceptual thinking, whilst critically evaluating my performance in achieving designs practically. I have strived for innovation but still need to work on how a resolve my ideas. The way drawings and models communicate my concepts need to be more articulated so that the viewers understand my design. Overall, I still need to focus on my time-management as well as work efficiency. It has been a delight furthering my knowledge from last semester and discovering other skills. This semester has been a true learning curve for me and one that I will take on and remember. Furthermore, I have learnt a lot through our presentations. This semester has truly widened my love for architecture and is a fitting end to my first year at university

Real-world clinical experience with long-term miglustat maintenance therapy in type 1 Gaucher disease: the ZAGAL project

There are few published data from real-world clinical experience with miglustat, an oral inhibitor of glucosylceramide synthase, in type 1 Gaucher disease. This study suggests that miglustat is an effective therapy for the long-term maintenance of patients with type 1 Gaucher disease previously stabilized with enzyme replacement therapy

A cellular and molecular basis for the selective desmopressin-induced ACTH release in cushing disease patients: Key role of AVPR1b receptor and potential therapeutic implications

Luque, Raúl M. et al.[Context] Desmopressin is a synthetic agonist of vasopressin receptors (AVPRs). The desmopressin stimulation test is used in the diagnosis and postsurgery prognosis of Cushing disease (CD). However, the cellular and molecular mechanisms underlying the desmopressin-induced ACTH increase in patients with CD are poorly understood. [Objective] The objectives of this study were to determine, for the first time, whether desmopressin acts directly and exclusively on pituitary corticotropinoma cells to stimulate ACTH expression/release and to elucidate the cellular and molecular mechanisms involved in desmopressin-induced ACTH increase in CD.[Design] A total of 8 normal pituitaries (NPs), 23 corticotropinomas, 14 nonfunctioning pituitary adenomas, 17 somatotropinomas, and 3 prolactinomas were analyzed for AVPR expression by quantitative real-time RT-PCR. Primary cultures derived from corticotropinomas, nonfunctioning pituitary adenomas, somatotropinomas, prolactinomas, and NPs were treated with desmopressin, and ACTH secretion/expression, [Ca2+]i kinetics, and AVPR expression and/or proliferative response were evaluated. The relationship between AVPR expression and plasma adrenocorticotropin/cor-tisol levels obtained from desmopressin tests was assessed.[Results] Desmopressin affects all functional parameters evaluated in corticotropinoma cells but not in NPs or other pituitary adenomas cells. These effects might be due to the dramatic elevation of AVPR1b expression levels found in corticotropinomas. In line with this notion, the use of an AVPR1b antagonist completely blocked desmopressin stimulatory effects. Remarkably, only AVPR1b expression was positively correlated with elevated plasma adrenocorticotropin levels in corticotropinomas.[Conclusions] The present results provide a cellular and molecular basis to support the desmopressin stimulation test as a reliable, specific test for the diagnosis and postsurgery prognosis of CD. Furthermore, our data indicate that AVPR1b is responsible for the direct/exclusive desmopressin stimulatory pituitary effects observed in CD, thus opening the possibility of exploring AVPR1b antagonists as potential therapeutic tools for CD treatment. Copyright © 2013 by The Endocrine Society.Funding organizations are Junta de Andalucia, Ministerios de Economía y Competitividad y Sanidad, Servicios Sociales e Igualdad, Ciber, Merck Serono, ISCIII (Spain).Peer Reviewe