The androgen receptor and signal-transduction pathways in hormone-refractory prostate cancer. Part 1: modifications to the androgen receptor

Prostate cancer is the second most common male malignancy in the western world an increasing incidence in an ageing population. Treatment of advanced prostate cancer relies on androgen deprivation. Although the majority of patients initially respond favourably to androgen deprivation therapy, the mean time to relapse is 12-18 months. Currently there are few treatments available for men who have developed resistance to hormone therapy, due to the lack of understanding of the molecular mechanisms underlying development of this disease. Recently, however, major advances have been made in understanding both androgen receptor (AR) dependent and independent pathways which promote development of hormone resistant prostate cancer. This review will focus on modifications to the AR and associated pathways. Molecular modifications to the androgen receptor itself, e.g. mutations and/or amplification, although involved in the development of hormone resistance cannot explain all cases. Phosphorylation of AR, via either Ras/MAP kinase or PI3K/Akt signal transduction pathways, have been shown to activate AR in both a ligand (androgen) dependent and independent fashion. During this review we will discuss the clinical evidence to support AR dependent pathways as mediators of hormone resistance

Attenuation of choroidal tickness in patients with Alzheimer disease: evidence from an Italian prospective study

INTRODUCTION: To compare the 12-month choroidal thickness (CT) change between Alzheimer disease (AD) patients and normal subjects. METHODS: In this prospective, observational study, 39 patients with a diagnosis of mild to moderate AD and 39 age-matched control subjects were included. All the subjects underwent neuropsychological (Mini Mental State Examination, Alzheimer disease Assessment Scale-Cognitive Subscale, and the Clinical Dementia Rating Scale) and ophthalmological evaluation, including spectral domain optical coherence tomography, at baseline and after 12 months. CT was measured manually using the caliper tool of the optical coherence tomography device. RESULTS: After 12 months, AD patients had a greater reduction of CT than controls (P≤0.05, adjusted for baseline CT, age, sex, axial length, and smoking). DISCUSSION: CT in patients with AD showed a rate of thinning greater than what could be expected during the natural course of aging

Lorenz integrable system moves \`a la Poinsot

A transformation is derived which takes Lorenz integrable system into the well-known Euler equations of a free-torque rigid body with a fixed point, i.e. the famous motion \`a la Poinsot. The proof is based on Lie group analysis applied to two third order ordinary differential equations admitting the same two-dimensional Lie symmetry algebra. Lie's classification of two-dimensional symmetry algebra in the plane is used. If the same transformation is applied to Lorenz system with any value of parameters, then one obtains Euler equations of a rigid body with a fixed point subjected to a torsion depending on time and angular velocity. The numerical solution of this system yields a three-dimensional picture which looks like a "tornado" whose cross-section has a butterfly-shape. Thus, Lorenz's {\em butterfly} has been transformed into a {\em tornado}.Comment: 14 pages, 6 figure

Biological applications of synchrotron radiation infrared spectromicroscopy.

Extremely brilliant infrared (IR) beams provided by synchrotron radiation sources are now routinely used in many facilities with available commercial spectrometers coupled to IR microscopes. Using these intense non-thermal sources, a brilliance two or three order of magnitude higher than a conventional source is achievable through small pinholes (<10 mu m) with a high signal to-noise ratio. IR spectroscopy is a powerful technique to investigate biological systems and offers many new imaging opportunities. The field of infrared biological imaging covers a wide range of fundamental issues and applied researches such as cell imaging or tissue imaging. Molecular maps with a spatial resolution down to the diffraction limit may be now obtained with a synchrotron radiation IR source also on thick samples. Moreover, changes of the protein structure are detectable in an IR spectrum and cellular molecular markers can be identified and used to recognize a pathological status of a tissue. Molecular structure and functions are strongly correlated and this aspect is particularly relevant for imaging. We will show that the brilliance of synchrotron radiation IR sources may enhance the sensitivity of a molecular signal obtained from small biosamples, e.g., a single cell, containing extremely small amounts of organic matter. We will also show that SR IR sources allow to study chemical composition and to identify the distribution of organic molecules in cells at submicron resolution is possible with a high signal-to-noise ratio. Moreover, the recent availability of two-dimensional IR detectors promises to push forward imaging capabilities in the time domain. Indeed, with a high current synchrotron radiation facility and a Focal Plane Array the chemical imaging of individual cells can be obtained in a few minutes. Within this framework important results are expected in the next years using synchrotron radiation and Free Electron Laser (FEL) sources for spectro-microscopy and spectral-imaging, alone or in combination with Scanning Near-field Optical Microscopy methods to study the molecular composition and dynamic changes in samples of biomedical interest at micrometric and submicrometric scales, respectively. (c) 2012 Elsevier Inc. All rights reserved

Development of a CO2 sensor for extracorporeal life support applications

Measurement of carbon dioxide (CO2) in medical applications is a well-established method for monitoring patient’s pulmonary function in a noninvasive way widely used in emergency, intensive care, and during anesthesia. Even in extracorporeal-life support applications, such as Extracorporeal Carbon Dioxide Removal (ECCO2R), Extracorporeal Membrane Oxygenation (ECMO), and cardiopulmonary by-pass (CPB), measurement of the CO2 concentration in the membrane oxygenator exhaust gas is proven to be useful to evaluate the treatment progress as well as the performance of the membrane oxygenator. In this paper, we present a new optical sensor specifically designed for the measurement of CO2 concentration in oxygenator exhaust gas. Further, the developed sensor allows measurement of the gas flow applied to the membrane oxygenator as well as the estimation of the CO2 removal rate. A heating module is implemented within the sensor to avoid water vapor condensation. Effects of temperature on the sensor optical elements of the sensors are disclosed, as well as a method to avoid signal–temperature dependency. The newly developed sensor has been tested and compared against a reference device routinely used in clinical practice in both laboratory and in vivo conditions. Results show that sensor accuracy fulfills the requirements of the ISO standard, and that is suitable for clinical applications

Self-sealing posterior scleral perforation in airgun ocular trauma, surgical tip: A case report

Background: Intraorbital metallic foreign bodies have varied clinical presentations. Here, we report the unusual case of intraoperative evidence of spontaneously healed posterior scleral perforation in a severe ballistic trauma without previous instrumental signs of penetrating wound and complete visual restoration after surgery. Case presentation: The patient was hit by several lead hunting pellets in the chest, abdomen, limbs, face and orbit. Computed Tomography (CT) images revealed the presence of a pellet within the orbitary cavity, close to the optic nerve, with no signs of penetrating ocular wound. While performing vitrectomy for severe vitreous hemorrhage, a point of strong adherence between a old hemorrhage and retinal surface was identified and managed conservatively, as it was attributed to trauma related-impact area. So, lead foreign body took an unusual trajectory impacting the globe and finally lodging back in the deep orbitary cavity, in absence of significant ocular injury and with visual prognosis preservation. Conclusions: Our findings provide further information on orbital injuries from airguns, a theme of growing popularity and concern. Intraoperative recognition of hardly removable old hemorrhagic clot as self-blockage site of posterior scleral penetrating trauma, allowed for surgical stabilization and minimal solicitation of the area to avoid inadvertent perforation

Androgen receptor mutations in prostate cancer

We analyzed the frequency and relevance of mutations in the coding region of the androgen receptor (AR) in genomic DNA extracted from 137 specimens of prostate cancer. The specimens were obtained from the primary tumors of patients affected by stage B disease [15 nonmicrodissected (group 1A) and 84 microdissected (group 1B)] and from the metastatic deposits of individuals with stage D1 disease [8 nonmicrodissected (group 2A) and 30 microdissected (group 2B)] who had not undergone androgen ablation therapy. The study was conducted by PCR-single strand conformational polymorphism (SSCP) analysis of exons 2-8 in the four groups and direct sequence analysis of exon 1 in group 1B. As positive and negative controls, we used genomic DNA extracted from genital skin fibroblasts of patients affected by various forms of androgen resistance with known mutations in the AR. To control for genetic instability, PCR-SSCP analysis of exon 2 of the human progesterone receptor was carried out on each specimen. The overall number of mutations detected was 11 (8%). No mutations were detected in any of the 99 patients with stage B disease. Eleven mutations were detected in exons 2-8 in 8 of the 38 patients with stage D1 disease (all in group 2B). Simultaneous analysis of exon 2 of the progesterone receptor was carried out, and no SSCP changes were identified. These data suggest that AR mutations are rare and presumably do not play a role in the initial phase of prostatic carcinogenesis. The presence of a significant number of AR mutations in metastatic disease indicates that mutations of this molecule may play a role in the most advanced phases of the natural history of this disease, either by facilitating growth or acquisition of the metastatic phenotype

First record of Acanthurus chirurgus (Perciformes: Acanthuridae) in the Mediterranean Sea, with some distributional notes on Mediterranean Acanthuridae

The occurrence of the doctorfish Acanthurus chirurgus is reported for the first time in the Mediterranean Sea, off Elba Island, Tyrrhenian Sea (42.726667° N, 10.434444° E). This record is tentatively related to aquarium release. The occurrence of Acanthuridae in the Mediterranean Sea is briefly reviewed, and some distributional notes on Acanthurus coeruleus and Acanthurus monroviae in the Mediterranean are provided

Molybdenum sputtering film characterization for high gradient accelerating structures

Technological advancements are strongly required to fulfill the demands of new accelerator devices with the highest accelerating gradients and operation reliability for the future colliders. To this purpose an extensive R&D regarding molybdenum coatings on copper is in progress. In this contribution we describe chemical composition, deposition quality and resistivity properties of different molybdenum coatings obtained via sputtering. The deposited films are thick metallic disorder layers with different resistivity values above and below the molibdenum dioxide reference value. Chemical and electrical properties of these sputtered coatings have been characterized by Rutherford backscattering, XANES and photoemission spectroscopy. We will also present a three cells standing wave section coated by a molybdenum layer $\sim$ 500 nm thick designed to improve the performance of X-Band accelerating systems.Comment: manuscript has been submitted and accepted by Chinese Physics C (2012

Lie point symmetries and first integrals: the Kowalevsky top

We show how the Lie group analysis method can be used in order to obtain first integrals of any system of ordinary differential equations. The method of reduction/increase of order developed by Nucci (J. Math. Phys. 37, 1772-1775 (1996)) is essential. Noether's theorem is neither necessary nor considered. The most striking example we present is the relationship between Lie group analysis and the famous first integral of the Kowalevski top.Comment: 23 page