Controlled-release oxycodone and pregabalin in the treatment of neuropathic pain: results of a multicenter Italian study

Abstract AIMS: The aim of our study was to compare the efficacy, safety, and quality of life of combination therapy with controlled-release (CR) oxycodone plus pregabalin versus monotherapy with either CR oxycodone or pregabalin in patients with neuropathic pain. MATERIALS AND METHODS: Patients with moderate to severe neuropathic pain, despite the use of various pharmacologic treatments prior to study entry, were enrolled (n = 409) and treated with CR oxycodone plus pregabalin (n = 169), CR oxycodone (n = 106), and pregabalin (n = 134). Pain intensity was rated on an 11-point numerical rating scale (NRS). RESULTS: The combination of CR oxycodone plus pregabalin and CR oxycodone monotherapy were both more effective for alleviating neuropathic pain than pregabalin monotherapy (reduction in NRS value: 80, 76, and 46%, respectively; p </= 0.003). Significantly greater improvements from baseline in quality of life were reported with combination therapy than with monotherapy (p = 0.0009). At the end of treatment, the majority (91.2%) of patients receiving CR oxycodone plus pregabalin found that the treatment had been 'effective' or 'very effective'. Combination therapy also allowed a dose reduction of both agents (22% for CR oxycodone and 51% for pregabalin) compared with the dosages of the respective monotherapies. Combination therapy had a superior safety profile compared with pregabalin monotherapy. CONCLUSIONS: The combination of CR oxycodone plus pregabalin may represent a valuable addition to the existing pharmacotherapy for neuropathic pain and warrants further investigation

Gerir a diversidade: contributos da aprendizagem cooperativa para a construção de salas de aula inclusivas

The action-research we have held at the primary education, in a school placed near the town of Tomar, in 2009-2010, under the master's degree in Special Education, was the starting point for writing this article. The research had as main objective to promote the successful learning of a heterogeneous group of students, where a child considered with longstanding special educational needs is included – diagnosis of galactosaemia and cognitive impairment. Starting from the educational context of a particular classroom of 2nd and 3rd grades, where we were working as special education teacher, we had created an inclusive learning environment for each student in the class. Through effective collaboration between fellow teachers, we generated changes in methodologies, breaking with some traditional practices in the classroom, when regular teachers and special education are in the same learning space. By a systematic implementation of cooperative learning strategies among students, and applying qualitative data gathering techniques of research, before and after the intervention – interview, naturalistic observation, sociometry and documental research –, we have increased the quality and quantity of learning and promoted another way of ‘looking to’ the difference

Novel regulators of PrPC expression as potential therapeutic targets in prion diseases

Introduction: Prion diseases are rare and fatal neurodegenerative disorders. The key molecular event in these disorders is the misfolding of the physiological form of the cellular prion protein, PrPC, leading to the accumulation of a pathological isoform, PrPSc, with unique features. Both isoforms share the same primary sequence, lacking detectable differences in posttranslational modification, a major hurdle for their biochemical or biophysical independent characterization. The mechanism underlying the conversion of PrPC to PrPSc is not completely understood, so finding an effective therapy to cure prion disorders is extremely challenging. Areas covered: This review discusses the strategies for decreasing prion replication and throws a spotlight on the relevance of PrPC in the prion accumulation process. Expert opinion: PrPC is the key substrate for prion pathology; hence, the most promising therapeutic approach appears to be the targeting of PrPC to block the production of the infectious isoform. The use of RNA interference and antisense oligonucleotide technologies may offer opportunities for treatment because of their success in clinical trials for other neurodegenerative diseases

Controlled-release oxycodone and pregabalin in the treatment of neuropathic pain: results of a multicenter Italian study

Aims: The aim of our study was to compare the efficacy, safety, and quality of life of combination therapy with controlled-release (CR) oxycodone plus pregabalin versus monotherapy with either CR oxycodone or pregabalin in patients with neuropathic pain. Materials and Methods: Patients with moderate to severe neuropathic pain, despite the use of various pharmacologic treatments prior to study entry, were enrolled (n = 409) and treated with CR oxycodone plus pregabalin (n = 169), CR oxycodone (n = 106), and pregabalin (n = 134). Pain intensity was rated on an 11-point numerical rating scale (NRS). Results: The combination of CR oxycodone plus pregabalin and CR oxycodone monotherapy were both more effective for alleviating neuropathic pain than pregabalin monotherapy ( reduction in NRS value: 80, 76, and 46%, respectively; p <= 0.003). Significantly greater improvements from baseline in quality of life were reported with combination therapy than with monotherapy ( p = 0.0009). At the end of treatment, the majority (91.2%) of patients receiving CR oxycodone plus pregabalin found that the treatment had been 'effective' or 'very effective'. Combination therapy also allowed a dose reduction of both agents (22% for CR oxycodone and 51% for pregabalin) compared with the dosages of the respective monotherapies. Combination therapy had a superior safety profile compared with pregabalin monotherapy. Conclusions: The combination of CR oxycodone plus pregabalin may represent a valuable addition to the existing pharmacotherapy for neuropathic pain and warrants further investigation. Copyright (c) 2008 S. Karger AG, Base

In silico/in vitro screening and hit evaluation identified new phenothiazine anti-prion derivatives

Prion diseases or transmissible spongiform encephalopathies (TSEs) are a group of rare neurodegenerative disorders. TSEs are characterized by the accumulation of prions (PrPSc) that represent pathological isoforms of the physiological cellular prion protein PrPC. Although the conversion of PrPC to PrPSc is still not completely understood, blocking this process may lead to develop new therapies. Here, we have generated a pharmacophore model, based on anti-prion molecules reported in literature to be effective in phenotypic assay. The model was used to conduct a virtual screen of commercial compound databases that selected a small library of ten compounds. These molecules were then screened in mouse neuroblastoma cell line chronically infected with prions (ScN2a) after excluding neurotoxicity. 1 has been identified as the therapeutic hit on the basis of the following evidence: chronic treatments of ScN2a cells using 1 eliminate PrPSc loaded in both Western blotting analysis and Real-Time Quaking-Induced Conversion (RT-QuIC) assay. We also proposed the mechanism of action of 1 by which it has the ability to bind PrPC and consequentially blocks prion conversion. Herein we describe the results of these efforts