IP Strategy in the Open Innovation Era: The Case Of Collaborative NPD

The most recent literature as well as the practice of companies are bringing into evidence that ensuring appropriability is very difficult, in the context of open innovation. The purpose of this paper is to study this problem, and, in particular, it is analyzed the role of organizational and managerial mechanisms in reinforcing the effectiveness of other IPPMs in collaborative NPD. The paper is based upon literature analysis and a multiple case study, involving three companies, and sheds some light on the specific organizational and managerial interventions that can be introduced within companies in order to improve the effectiveness of the IP strategy in collaborative NPD

A comparison between in vivo and ex vivo HR-MAS H-1 MR spectra of a pediatric posterior fossa lesion

The present case report was aimed at identifying the molecular profile characteristic of a primitive neuroectodermal tumor (PNET) in a 3-year-old child affected by a lesion localized in the cerebellar region. The histological diagnosis was medulloblastoma. In vivo single voxel H-1 magnetic resonance spectroscopy (MRS) shows high specificity in detecting the main metabolic alterations in the primitive cerebellar lesion; a very high amount of the choline-containing compounds and very low level of creatine derivatives and N-acetylaspartate. Ex vivo high resolution magic angle spinning (HR-MAS) H-1 magnetic resonance spectroscopy, performed at 9.4 Tesla on the neoplastic specimen collected during surgery, allows for the unambiguous identification of several metabolites giving a more in-depth evaluation of the metabolic pattern of the lesion. The ex vivo HR-MAS MR spectra show that the spectral detail is much higher than that obtained in vivo and that, for example, myo-inositol, taurine and phosphorylethanolamine contribute to the in vivo signal at 3.2 ppm, usually attributed to choline-containing compounds. In addition, the spectroscopic data appear to correlate with some morphological features of the medulloblastoma. Consequently, the present study shows that ex vivo HR-MAS H-1 MRS is able to strongly improve the clinical possibility of in vivo MRS and can be used in conjunction with in vivo spectroscopy for clinical purposes

A kinetic binding study to evaluate the pharmacological profile of a specific leukotriene C-4 binding site not coupled to contraction in human lung parenchyma

We report the identification of a novel pharmacological profile for the leukotriene (LT)C-4 binding site we previously identified in human lung parenchyma (HLP). We used a series of classic cysteinyl-LT (CysLT)(1) receptor antagonists belonging to different chemical classes and the dual CysLT(1)-CysLT(2) antagonist BAY u9773 for both binding and functional studies. Because the presence of (S)-decyl-glutathione interfered with cysteinyl-LT binding, with a kinetic protocol we avoided the use of this compound. By means of heterologous dissociation time courses, we demonstrated that zafirlukast, iralukast, and BAY u9773 selectively competed only for H-3-LTD4 binding sites, whereas pobilukast, pranlukast, and CGP 57698 dissociated both H-3-LTC4 and H-3-LTD4 from their binding sites. Thus, with binding studies, we have been able to identify a pharmacological profile for LTC4 distinct from that of LTD4 receptor (CysLT(1)) in HLP. On the contrary, in functional studies, all of the classic antagonists tested were able to revert both LTC4- and LTD4-induced contractions of isolated HLP strips. Thus, LTD4 and LTC4 contract isolated HLP strips through the same CysLT1 receptor. The results of kinetic binding studies, coupled to a sophisticated data analysis, confirm our hypothesis that HLP membranes contain two cysteinyl-LT high-affinity binding sites with different pharmacological profiles. In functional studies, however, LTD4- and LTC4-induced contractions are mediated by the same CysLT(1) receptor. In conclusion, the specific LTC4 high-affinity binding site cannot be classified as one of the officially recognized CysLT receptors, and it is not implicated in LTC4-induced HLP strip contractions

Label-Free Optical Sensing and Medical Grade Resins: An Advanced Approach to Investigate Cell–Material Interaction and Biocompatibility

: The Corning Epic® label-free (ELF) system is an innovative technology widely used in drug discovery, immunotherapy, G-protein-associated studies, and biocompatibility tests. Here, we challenge the use of ELF to further investigate the biocompatibility of resins used in manufacturing of blood filters, a category of medical devices representing life-saving therapies for the increasing number of patients with kidney failure. The biocompatibility assays were carried out by developing a cell model aimed at mimicking the clinical use of the blood filters and complementing the existing cytotoxicity assay requested by ISO10993-5. Experiments were performed by putting fibroblasts in both direct contact with two types of selected resins, and indirect contact by means of homemade customized well inserts that were precisely designed and developed for this technology. For both types of contact, fibroblasts were cultured in medium and human plasma. ELF tests confirmed the biocompatibility of both resins, highlighting a statistically significant different biological behavior of a polyaromatic resin compared to control and ion-exchanged resin, when materials were in indirect contact and soaking with plasma. Overall, the ELF test is able to mimic clinical scenarios and represents a promising approach to investigate biocompatibility, showing peculiar biological behaviors and suggesting the activation of specific intracellular pathways

Expression of prostacyclin receptors in luteinizing hormone-releasing hormone immortalized neurons: role in the control of hormone secretion

PGs of the E series are involved in the control of LHRH secretion. The present experiments were conducted to clarify whether PGI2 (prostacyclin) might be also involved in such a control, using multiple methodological approaches on immortalized LHRH-secreting neurons. A RT-PCR procedure to detect mouse PGI2 receptor (IP) messenger RNA was first applied, and the results obtained showed the presence of a specific transcript in two cell lines of immortalized LHRH neurons (GT1-1 and GN11 cell lines). Receptor binding assays on membrane preparations from GT1-1 cells showed the presence of a single specific and saturable class of binding sites (Kd = 4.6 nM; 10,000 sites/cell) for [3H]iloprost, a stable analog of PGI2. Competition experiments showed that the binding sites labeled by [3H]iloprost possess the pharmacological characteristics of IP receptors. In functional studies, PGI2 and its analogs, iloprost and cicaprost, were able to stimulate LHRH release from the GT1-1 cells with elevated potencies (EC50 = 0.6-4.3 nM); PGE1 was only slightly less active (EC50 = 28.5 nM), whereas PGE2, considered the major PG involved in LHRH secretion, was poorly effective (EC50 = 921 nM). The relative potencies (EC50) of these compounds in stimulating the intracellular accumulation of cAMP were in line with their LHRH-releasing activities. In conclusion, these results indicate that immortalized LHRH-secreting neurons express IP receptors through which PGI2 may exert relevant effects on LHRH release

Novel bioprinted 3D model to human fibrosis investigation

Fibrosis is shared in multiple diseases with progressive tissue stiffening, organ failure and limited therapeutic options. This unmet need is also due to the lack of adequate pre-clinical models to mimic fibrosis and to be challenged novel by anti-fibrotic therapeutic venues. Here using bioprinting, we designed a novel 3D model where normal human healthy fibroblasts have been encapsulated in type I collagen. After stimulation by Transforming Growth factor beta (TGFβ), embedded cells differentiated into myofibroblasts and enhanced the contractile activity, as confirmed by the high level of α − smooth muscle actin (αSMA) and F-actin expression. As functional assays, SEM analysis revealed that after TGFβ stimulus the 3D microarchitecture of the scaffold was dramatically remolded with an increased fibronectin deposition with an abnormal collagen fibrillar pattern. Picrius Sirius Red staining additionally revealed that TGFβ stimulation enhanced of two logarithm the collagen fibrils neoformation in comparison with control. These data indicate that by bioprinting technology, it is possible to generate a reproducible and functional 3D platform to mimic fibrosis as key tool for drug discovery and impacting on animal experimentation and reducing costs and time in addressing fibrosis

Short-term efficacy and safety of betamethasone valerate 2.25 mg medicated plaster in patients with chronic lateral epicondylitis: Results of a randomised, double blind, placebo-controlled study

Background. This placebo-controlled, double-blind study evaluated the short-term effects of betamethasone valerate (BMV) 2.25mg medicated plaster in patients with chronic lateral elbow tendinopathy (LET). Methods. Adult outpatients with LET and on-movement pain intensity ≥50 mm at a 0-100mm visual analogue scale (VAS) were randomised to receive BMV (N=101) or placebo (N=98), 12 hours/day for 4 weeks. Pain decrease from baseline to Day 28 was the primary endpoint. Other endpoints were: patient-rated tennis elbow evaluation (PRTEE), use of rescue paracetamol, tolerability at the application site. Results. Decrease in mean pain VAS from baseline to Day 28 was significantly higher with BMV vs. placebo: the difference between groups (intent-to-treat) was-8.57 mm (95% CI:-16.19 to-0.95 mm; p=0.028). Higher pain decreases in the BMV group over placebo were reported weekly during each control visit and daily in patients’ measurements on diaries. Treatment with BMV also led to higher decreases vs. placebo in PRTEE total, pain and functional disability score. Use of paracetamol was minimal. BMV plaster was well tolerated for general and local adverse events. Conclusions. BMV 2.25mg plaster was superior to placebo and well tolerated in patients with painful chronic LET

Nuclear receptor ligands induce TREM-1 expression on dendritic cells: analysis of their role in tumors

Dendritic cells (DCs) initiate adaptive immune responses after their migration to secondary lymphoid organs. The LXR ligands/oxysterols and the RXR ligand 9-cis Retinoic Acid (9-cis RA) were shown to dampen DC migration to lymphoid organs through the inhibition of CCR7 expression. We performed transcriptomics of DCs undergoing maturation in the presence of the LXR ligand 22R-Hydroxycholesterol (22R-HC). The analysis highlighted more than 1500 genes modulated by 22R-HC treatment, including the triggering receptor expressed on myeloid cells (TREM)-1, which was found markedly up-regulated. We tested the effect of other nuclear receptor ligands (NRL) and we reported the induction of TREM-1 following RXR, RAR and VDR activation. From a functional point of view, triggering of TREM-1 induced by retinoids increased TNF\u3b1 and IL-1\u3b2 release, suggesting an active role of NRL-activated TREM-1+ DCs in inflammation-driven diseases, including cancer. Consistently with this hypothesis we detected DCs expressing TREM-1 in pleural effusions and ascites of cancer patients, an observation validated by the induction of TREM-1, LXR and RAR target genes when monocyte-DCs were activated in the presence of tumor-conditioned fluids. Finally, we observed a better control of LLC tumor growth in Trem-1 12/- bone marrow chimera mice as compared to wild type chimera mice. Future studies will be necessary to shed light on the mechanism of TREM-1 induction by distinct NRL, and to characterize the role of TREM-1+ DCs in tumor growth