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Nieto F.R.,University of Granada | Nieto F.R.,Kings College London | Cendan C.M.,University of Granada | Canizares F.J.,University of Granada | And 4 more authors.
Molecular Pain | Year: 2014

Background: Paclitaxel, a widely-used antineoplastic drug, produces a painful peripheral neuropathy that in rodents is associated with peripheral-nerve mitochondrial alterations. The sigma-1 receptor (σ1R) is a ligand-regulated molecular chaperone involved in mitochondrial calcium homeostasis and pain hypersensitivity. This receptor plays a key role in paclitaxel-induced neuropathic pain, but it is not known whether it also modulates mitochondrial abnormalities.In this study, we used a mouse model of paclitaxel-induced neuropathic pain to test the involvement of the σ1R in the mitochondrial abnormalities associated with paclitaxel, by using genetic (σ1R knockout mice) and pharmacological (σ1R antagonist) approaches.Results: Paclitaxel administration to wild-type (WT) mice produced cold- and mechanical-allodynia, and an increase in the frequency of swollen and vacuolated mitochondria in myelinated A-fibers, but not in C-fibers, of the saphenous nerve. Behavioral and mitochondrial alterations were marked at 10 days after paclitaxel-administration and had resolved at day 28. In contrast, paclitaxel treatment did not induce allodynia or mitochondrial abnormalities in σ1R knockout mice. Moreover, the prophylactic treatment of WT mice with BD-1063 also prevented the neuropathic pain and mitochondrial abnormalities induced by paclitaxel.Conclusions: These results suggest that activation of the σ1R is necessary for development of the sensory nerve mitochondrial damage and neuropathic pain produced by paclitaxel. Therefore, σ1R antagonists might have therapeutic value for the prevention of paclitaxel-induced neuropathy. © 2014 Nieto et al.; licensee BioMed Central Ltd. Source

Rodriguez Arroyo L.A.,Gerencia de Atencion Primaria El Bierzo | Pinto Sala X.,Hospital Universitario Of Bellvitge | Coca Payeras A.,Institute Clinic Of Medicina I Dermatologia Icmid | Rius Tarruella J.,ESTEVE
Clinica e Investigacion en Arteriosclerosis | Year: 2014

Introduction: Evaluating the therapeutical adherence as well as the patient' satisfaction with the treatment should be considered to optimize lipidic control. The REINA Study evaluates the grade of satisfaction in dyslipidemic patients treated with pitavastatin. Methods: The current study was observational, descriptive, transversal and multi-centric with patients from our country only. The following data were collected in each case: Morisky-Green test and TSQM-9 for patients older than 18. years old, with dyslipidemia treated with pitavastatin in the last 12 weeks. Results: We studied 6,489. patients (60.0% males) from Primary Health (52.7%) and Specialised Health (47.3%), with age (mean). =. 60.9. ±. 11.2. years by aleatory sampling. 72.3% of patients achieved an adequate control with 2. mg/day of pitavastatin. General satisfaction with the treatment was 73.20 points (95%. CI: 58.17-87.23). Patients who followed the treatment (65%) showed better data of satisfaction with the drug (77.70 [95%. CI: 65.20-90.20]), of global satisfaction (75.00 [95%. CI: 61.50-88.50]) and their satisfaction with the drug efficiency was higher (72.50 [95%. CI: 57.70-87.30]) than in the patients who did not finish the treatment (72.70 [95%. CI: 59.30-85.74]; 68.5 [95%. CI: 53.20-83.80] and 67.80 [95%. CI: 53.70-81.90], respectively), P<. .0001, without any difference between the two primary care systems. Conclusions: The validation of the satisfaction is a crucial indicator in the evaluation of the services offered in health. Patients with the highest grade of satisfaction present better therapeutical adherence, and such a relation is bidirectional. The individuals who are satisfied and who followed the treatment obtained better clinical results. Pitavastatin is an effective therapeutic alternative for patients with dyslipidemia. © 2013 Sociedad Española de Arteriosclerosis. Source

Pallicer J.M.,University of Barcelona | Calvet C.,ESTEVE | Port A.,ESTEVE | Roses M.,University of Barcelona | And 2 more authors.
Journal of Chromatography A | Year: 2012

A reorted chromatographic method to determine the 1-octanol/water partition coefficient (logP o/w) has been used to estimate the lipophilicity of 33 drugs with diverse structures and functionalities, including neutral, acid, basic, and amphoteric compounds. The applicability of the chromatographic method has been extended to the UHPLC technique, and the results obtained were compared to those obtained from conventional HPLC. No significant difference between the results obtained by both techniques is noticed. Thus, the suitability of UHPLC, which involves shorter run times, for lipophilicity assessment is demonstrated. In order to show the consistency of this chromatographic method, the logP o/w values of those drugs which have acid-base properties have been also determined by potentiometry, and the final results have been compared with both values derived from the chromatographic method and the ones from the literature. © 2012 Elsevier B.V. Source

Bura A.S.,University Pompeu Fabra | Guegan T.,University Pompeu Fabra | Zamanillo D.,ESTEVE | Vela J.M.,ESTEVE | Maldonado R.,University Pompeu Fabra
European Journal of Pain (United Kingdom) | Year: 2013

Background: The treatment of neuropathic pain is unsatisfactory at the present moment and the sigma 1 receptor has been identified as a new potential target for neuropathic pain. The aim of this study was to use an operant self-administration model to reveal the potential interest of a new sigma 1 receptor antagonist, S1RA, in chronic pain that was developed in mice by a partial ligation of the sciatic nerve. Methods: Once that chronic pain had reached a steady state, mice were trained to maintain an operant behaviour to self-administer S1RA. The possible abuse liability of the analgesic compound was determined by evaluating operant self-administration in sham-operated mice. The influence of S1RA on the anhedonic state related to chronic pain was also evaluated by measuring the preference for palatable drink (2% sucrose solution) using a recently validated and highly sensitive behavioural device. Results: Nerve-injured mice, but not sham-operated animals, acquired the operant responding to obtain S1RA (6 mg/kg/infusion). After 10 days of S1RA self-administration, neuropathic pain was significantly reduced in nerve-injured mice. In addition, an anhedonic state was revealed in nerve-injured mice by a decreased consumption of palatable drink, which was significantly attenuated by S1RA (25 mg/kg). Conclusions: These results reveal the analgesic efficacy of the sigma antagonist, S1RA, in neuropathic pain associated with an improvement of the emotional negative state and that was devoided of reinforcing effects. The operant responses evaluated in this new mouse model can have a high predictive value to estimate the clinical benefit/risk ratio of new analgesic compounds to treat chronic pain, such as S1RA. © 2012 European Federation of International Association for the Study of Pain Chapters. Source

Pallicer J.M.,University of Barcelona | Pascual R.,ESTEVE | Port A.,ESTEVE | Roses M.,University of Barcelona | And 2 more authors.
European Journal of Pharmaceutical Sciences | Year: 2013

The influence of the hydrogen bond acidity when the 1-octanol/water partition coefficient (log Po/w) of drugs is determined from chromatographic measurements was studied in this work. This influence was firstly evaluated by means of the comparison between the Abraham solvation parameter model when it is applied to express the 1-octanol/water partitioning and the chromatographic retention, expressed as the solute polarity p. Then, several hydrogen bond acidity descriptors were compared in order to determine properly the log Po/w of drugs. These descriptors were obtained from different software and comprise two-dimensional parameters such as the calculated Abraham hydrogen bond acidity A and three-dimensional descriptors like HDCA-2 from CODESSA program or WO1 and DRDODO descriptors calculated from Volsurf + software. The additional HOMO-LUMO polarizability descriptor should be added when the three-dimensional descriptors are used to complement the chromatographic retention. The models generated using these descriptors were compared studying the correlations between the determined log Po/w values and the reference ones. The comparison showed that there was no significant difference between the tested models and any of them was able to determine the log Po/w of drugs from a single chromatographic measurement and the correspondent molecular descriptors terms. However, the model that involved the calculated A descriptor was simpler and it is thus recommended for practical uses. © 2012 Elsevier B.V. All rights reserved. Source

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