NiKem Research

Baranzate, Italy

NiKem Research

Baranzate, Italy

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Sangster T.,Charles River Associates | Maltas J.,BASi | Struwe P.,Celerion | Hillier J.,Gen-Probe | And 27 more authors.
Bioanalysis | Year: 2012

The 5th Global CRO Council for Bioanalysis (GCC) meeting, held in Barcelona, Spain, in November 2011, provided a unique opportunity for CRO leaders to openly share opinions, perspectives and to agree on bioanalytical recommendations on incurred sample reproducibility in multi-analyte assays, regulation of quality assurance/bioanalytical consultants and regulatory requirements for GCP. © 2012 Future Science Ltd.


Lowes S.,Quintiles | Boterman M.,ABL | Doig M.,ABS Laboratories | Breda M.,Accelera | And 88 more authors.
Bioanalysis | Year: 2012

An open letter written by the Global CRO Council for Bioanalysis (GCC) describing the GCC survey results on stability data from co-administered and co-formulated drugs was sent to multiple regulatory authorities on 14 December 2011. This letter and further discussions at different GCC meetings led to subsequent recommendations on this topic of widespread interest within the bioanalytical community over the past 2 years. © 2012 Future Science Ltd.


Colombo M.,NiKem Research | Bianchi A.,Consorzio Interdisciplinare di Studi Biomolecolari ed Applicazioni Industriali CISI
Molecules | Year: 2010

In the last few years click chemistry reactions, and in particular coppercatalyzed cycloadditions, have been used intensively for the preparation of new bioconjugate molecules and materials applicable to biomedical and pharmaceutical areas. This review will be focused on conjugates of the tripeptide Arg-Gly-Asp formed by means of click chemistry reactions. This sequence is a well known binding motif for specific transmembrane proteins and is involved in cellular adhesion to the extracellular matrix, allowing the selective recognition of the biomolecule or polymer in which it is incorporated.


Fariello R.G.,Neurotune AG | Ghelardini C.,University of Florence | Di Cesare Mannelli L.,University of Florence | Bonanno G.,University of Genoa | And 4 more authors.
Neuropharmacology | Year: 2014

Dimiracetam, a bicyclic 2-pyrrolidinone derivative originally developed as cognition enhancer, is a member of the nootropic family for which anecdotal efficacy in models of neuropathic pain has been reported. Its antineuropathic activity was evaluated in established models of neuropathic pain induced by nerve injury, chemotherapy or MIA-induced osteoarthritis. Acutely, dimiracetam was very effective in models of antiretroviral drug induced painful neuropathy, oxaliplatin-induced hyperalgesia and in the MIA-osteoarthritis. Chronic dimiracetam dosing in the MIA and ART- induced models completely reverted hyperalgesia back to the level of healthy controls. Once reached, the maximal effect was maintained despite dose diminution and increased inter-dose interval. The effect of the last dose outlasted dimiracetam half-life longer than 12 times. In synaptosomal preparations, dimiracetam counteracted the NMDA-induced release of glutamate with highest potency in the spinal cord, possibly via NMDA receptor isoforms containing pH-sensitive GluN1 and GluN2A subunits. Dimiracetam appears to be a promising and safe treatment for neuropathic pain conditions for which there are very limited therapeutic options. © 2014 Elsevier Ltd. All rights reserved.


Villetti G.,Chiesi Farmaceutici SpA | Pastore F.,Chiesi Farmaceutici SpA | Bergamaschi M.,Chiesi Farmaceutici SpA | Bassani F.,Chiesi Farmaceutici SpA | And 20 more authors.
Journal of Pharmacology and Experimental Therapeutics | Year: 2010

The novel quaternary ammonium salt (3R)-3-[[[(3-fluorophenyl)[(3,4,5- trifluorophenyl)methyl]amino]carbonyl]oxy]-1-[2-oxo-2-(2-thienyl-)ethyl] -1-azoniabicyclo[2.2.2]octane bromide (CHF5407) showed subnanomolar affinities for human muscarinic M1 (hM1), M2 (hM2), and M3 (hM3) receptors and dissociated very slowly from hM3 receptors (t1/2 = 166 min) with a large part of the receptorial complex (54%) remaining undissociated at 32 h from radioligand washout. In contrast, [3H]CHF5407 dissociated quickly from hM2 receptors (t1/2 = 31 min), whereas [3H]tiotropium dissociated slowly from both hM3 (t1/2 = 163 min) and hM2 receptor (t1/2 = 297 min). In the guinea pig isolated trachea and human isolated bronchus, CHF5407 produced a potent (pIC50 = 9.0-9.6) and long-lasting (up to 24 h) inhibition of M3 receptor-mediated contractile responses to carbachol. In the guinea pig electrically driven left atrium, the M2 receptor-mediated inhibitory response to carbachol was recovered more quickly in CHF5407-pretreated than in tiotropium-pretreated preparations. CHF5407, administered intratracheally to anesthetized guinea pigs, potently inhibited acetylcholine (Ach)-induced bronchoconstriction with an ED50 value of 0.15 nmol/kg. The effect was sustained over a period of 24 h, with a residual 57% inhibition 48 h after antagonist administration at 1 nmol/kg. In conscious guinea pigs, inhaled CHF5407 inhibited Ach-induced bronchoconstriction for at least 24 h as did tiotropium at similar dosages. Cardiovascular parameters in anesthetized guinea pigs were not significantly changed by CHF5407, up to 100 nmol/kg i.v. and up to 1000 nmol/kg i.t. In conclusion, CHF5407 shows a prolonged antibronchospastic activity both in vitro and in vivo, caused by a very slow dissociation from M3 receptors. In contrast, CHF5407 is markedly short-acting at M2 receptors, a behavior not shared by tiotropium. Copyright © 2010 by The American Society for Pharmacology and Experimental Therapeutics.

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