An experimental study on dependence liability of zipeprol.

Zipeprol, a piperazine ethanol derivative, is a non-essential but widely used (paediatric) antitussive, which is not legally considered as being capable of creating dependence or abuse liability. A first group of experimental results was obtained assaying the displacement of 1 nM [3H]naloxone by zipeprol vs morphine on the rat brain homogenate fractions. A second group was carried out on the longitudinal muscle of guinea-pig ileum, using the field stimulation technique, either in the absence or in the presence of naloxone 1 x 10(-5)M or in the absence or in the presence of yohimbine 1 x 10(-5)M. Further investigations concerning the pharmacological and the biochemical characterization of the mechanisms involved in abuse liability were carried out by means of the in vitro inhibition of ACh response on the guinea-pig ileum preparation. The results indicate zipeprol as a moderate opioid agonist, which also shows a direct anticholinergic effect, independent of presynaptic alpha 2 interaction

Electrophysiological effects of a pumiliotoxin-B-like alkaloid derived from the skin of the Australian frog Pseudophryne coriacea.

Skin extracts of the Australian frog Pseudophryne coriacea (PsC) potentiate and prolong the bioelectric activity of various excitable tissues. When studied by electrophysiological means in a preparation of mouse diaphragm, PsC skin extracts did not affect the spontaneous acetylcholine (ACh) release. However, the indirect stimulation of the preparation in the presence of PsC skin extracts gave rise to a different profile of rhythmic activity showing afterpotentials and variable oscillatory activity. The action potential and the total sodium current recorded in the muscle fibre with the loose patch clamp method were not modified significantly by the alkaloid. Concentrations of PsC skin extract that did not cause repetitive activity, seemed to reduce slightly the quantal content of the evoked release of ACh. The resting potential of muscle fibres was not modified even by the highest PsC skin extract concentrations. These results suggest that the facilitation effects of PsC skin extracts could be due to intracellular mechanisms probably related to the control of the cytosolic calcium concentrations or to an increased excitability of the presynaptic biomembranes

Proof of concept of the structural health monitoring of framed structures by a novel combined experimental and theoretical approach

Summary One of the most important issues in engineering is the detection of structural damages. During its life cycle, a building, besides the exposure to operational and environmental forces, can be subjected to earthquakes or to other non-ordinary loads. These events may have a deep impact on the building safety, and thus, a continuous monitoring of the structure health conditions becomes desirable or even necessary in many cases. In this context, the usage of vibration-based structural health monitoring (SHM) systems is spreading from big infrastructures applications, like bridges, dams or skyscrapers, to the historical heritage and to public or residential buildings. The aim of this work is to propose a combined experimental and numerical methodology to perform the SHM of structures of the civil engineering lying in seismic hazard zones. A relatively low cost SHM prototype system based on this approach is developed. The data acquired by the system are provided to a finite element method (FEM) numerical model to detect the appearing, the rise and the distribution of local damages and to estimate a global damage level. The system has been tested and calibrated on a three-storey prototype model. The procedure for the estimation of the damage level is calibrated by comparing the experimental quantities measured during cyclic failure tests with the FEM model predictions. Copyright © 2015 John Wiley & Sons, Ltd

Up-to 5-year efficacy of pasireotide in a patient with Cushing's disease and pre-existing diabetes: literature review and clinical practice considerations.

Purpose Pasireotide is a multi-receptor-targeted somatostatin analogue approved in the EU and in the US for the treatment of adults with Cushing's disease (CD). Pasireotide has a safety profile similar to other somatostatin analogues with the exception of hyperglycemia. In this report and literature review, the current understanding of predicting a positive treatment response to pasireotide in CD and the management of diabetes mellitus (DM) during pasireotide treatment are discussed and analyzed. Case presentation We report a case of a 55-year-old woman with CD and DM who benefitted from long-term pasireotide. The patient, who was enrolled in a phase III trial of the drug, showed early clinical improvements with pasireotide [900 \u3bcg subcutaneously twice daily (bid)] but was classified as a non-responder as urinary free cortisol (UFC) levels, were not normalized. Continuation of pasireotide for 12 months at an increased dose (1,200 \u3bcg bid) normalized UFC levels and restored cortisol rhythm. The initial deterioration in her blood glucose was managed with insulin and metformin; however, after 12 months' treatment with pasireotide her DM was well controlled with oral hypoglycemic agents. Five years later, the patient is still receiving pasireotide (300 \u3bcg bid) with no loss of clinical or biochemical efficacy and with continued glycemic control. Conclusions This case presentation indicates that uncontrolled UFC levels during the first few months of pasireotide treatment as well as worsening of glycemic control in patients with CD and DM are not always predictive of the efficacy and tolerability and appears to support the long-term continuation of pasireotide

Diagnostic robot for vibro-acoustic measurements in accelerated life tests

The present paper outlines the application scenario which motivates the development of an autonomous mobile robot for mechanical diagnostics based on vibro-acoustic testing of electromechanical systems undergoing Accelerated Life Testing (ALT). The application for ALT of Washing Machines (WM) is demonstrated. Usually in ALTs laboratories hundreds of samples are tested in parallel, and the instrumentation of a huge number of stations with sophisticated noise and vibration test equipments would be too expensive. A mobile robot platform equipped with sensors for noise and vibration diagnostics (14 microphones array, Scanning Laser Doppler Vibrometer (SLDV), vision system and robot arm) opens the possibility to monitor in sequence all appliances under test. Data from microphones have been processed with a beam forming algorithm in order to increase the signal-to-noise ratio and to minimize the effects on the measurement of the appliances close the one under test, while an algorithm based on images pattern matching has been developed to enhance the repeatability of laser spot positioning on the products. In this paper, the main issues and problems related to the implementation of a vibro-acoustic analysis system on a mobile robot are discussed and its performances in terms of repeatability of measures, defects recognition through signal features extraction (e.g. faulty motors, bearings, etc…), are presented and discussed with reference to house-hold appliance testing. Tests have been carried out both in laboratory, with few WMs in controlled operating conditions and in a real ALT area in a washing machine factory

Fracture risk assessment before and after resolution of endogenous hypercortisolism: Is the FRAX(\uae) algorithm useful?

Purpose Fracture risk data following curative treatment of Cushing's syndrome (CS) are scarce and the role of bisphosphonates in bone recovery after remission is controversial. We evaluated the effects of hypercortisolism remission in bone recovery in CS. Then, we assessed if the FRAX (R) algorithm calculated before the cure can predict fracture risk after cure. Methods Thirty-six patients with CS were retrospectively investigated. Bone turnover markers, bone mineral density (BMD) at the lumbar spine (L1-L4) and left femur (both neck and total hip were considered), and fracture risk using FRAX (R) algorithm with femoral neck BMD were evaluated at diagnosis and after a median follow-up of 24 months (range 12-108 months) from hypercortisolism remission. Data about bone active therapy were analyzed. Results Hypercortisolism remission was associated with the improvement of all densitometric parameters and with the reduction of fracture risk. The percentage change in BMD and the fracture risk were not significantly different in bisphosphonate-treated vs. untreated patients. During follow-up, three fractured patients at baseline exhibited a new vertebral fracture. A baseline 10-year probability of major osteoporotic fractures (FRAX (R) Major) of 17 % was able to predict the occurrence of a new vertebral fracture during follow-up after cure with 100 % sensitivity, 77 % specificity, 81 % positive predictive value and 100 % negative predictive value. Conclusions Osteoporosis and fracture risk may be reversible after curative treatment of CS, regardless of bisphosphonate therapy. We suggest applying the FRAX (R) algorithm to all active CS patients using a baseline FRAX (R) Major of 17 % as "intervention threshold"