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Il Linguaggio della Ricerca (LdR) è un progetto nato a Bologna nel 2003 per suscitare l'interesse dei giovani nei confronti della ricerca scientifica, mediante un coinvolgimento nella divulgazione dei contenuti appresi, utilizzando l'italiano e l'inglese. Si è così creata una sinergia fra il mondo della Scuola e della Ricerca, integrando l'esperienza dei ricercatori, le capacità didattiche degli insegnanti delle Scuole Secondarie di I e II grado e la creatività degli studenti. Sito web: https://ldr-network.bo.cnr.it/

Background:RA is the most prevalent chronic inflammatory rheumatism, responsible of functional impairment.Objectives:To investigate the value of biological and imaging biomarkers on predicting good clinical response at 6 months, in RA patients initiating IV bDMARD.Methods:From 2008 to 2017, 317 RA patients fulfilling ACR 1987 and/or ACR-EULAR 2010 criteria for RA, initiated IV bDMARDs in our department of Rheumatology. Patients were excluded in cases of lack of information on disease activity assessment before and at 6 months of treatment and on immunological status and titers (ACPA, RF, ANA) at baseline. For patients receiving successive IV bDMARDs during this time period (n=30), a randomization permitted to select 1 treatment sequence for the analysis. On 173 patients eligible to the study, 4 were loss to follow-up and 14 stopped treatment due to adverse events before 6 months. Clinical, biological and imaging (US and RX) data were collected when available at baseline. US examination was performed on 12 joints (wrist, MCP2-3-5 and MTP2-3-5) with qualitative and quantitative evaluation on B mode and Power Doppler (PD) for synovitis, tenosynovitis and erosion. The modified Sharp/van der Heijde erosion score was performed by 2 independent readers blindly from clinical and US informations. Good clinical response was defined by a DAS 28 < 3.2 and/ or DAS 28 decrease > 1.2 at 6 months. Only variables with a pResults:On 155 RA patients, 11 present a disease duration < 2 year, 44 (28.3%) were on first line of IV bDMARDs and 111 patients received at least one IV bDMARD (mean 2.5 (1.3)).Table 1.Characteristics of the patients (n=155) at baselineVariablesN (%)Mean (SD)Clinical characteristicsAge (years)54.8 (12.2)Female113 (72.9)Disease duration (months)166.9 (118.8)DAS 285.2 (1)TreatmentCorticosteroids / dose (mg/day)99 (85.3)10.9 (6)Monotherapy56 (36.1)IV bDMARDAbatacept27 (17.4)Infliximab11 (7.1)Rituximab84 (54.2)Tocilizumab33 (21.3)ImmunologyACPA + /titer(IU)132 (85.2)618.5 (791.0)RF + /titer (IU/ml)114 (74.5)184.7 (351.3)ANA + / level87 (56.1)1453 (3836)RadiographySharp’s erosion score (n=110)49.4 (46.2)USNb Erosion (n=95)3.0 (2.3)Nb B mode Synovitis (n=128)6.0 (4.1)Nb PD+ Synovitis (n=130)4.8 (3.8)Nb B mode Tenosynovitis (n=129)1.6 (2)Nb PD+ Tenosynovitis (n=129)1.3 (2.1)At 6 months, 87 patients (56.1%) were in good clinical response. Predictive values of biomarkers are presented in table 2.Table 2.Variables predictive of a good clinical response at 6 monthsBiomarkersResponseMultivariate Logistic regression AnalysisAllN = 101Response(N=60)OR (CI95%)P valueImmunology RF +7551 (68.0%)5.1 (1.8-14.4)0.002 ACPA +8756 (64.4%) ANA +5536 (65.5%)Radiography Erosive RA7448 (64.9%)Ultrasonography Erosive RA8855 (62.5%) Nb B mode synovitis10160 (59.4%)1.2 (1.1-1.4)0.002 Nb PD+ synovitis10160 (59.4%)All qualitative variables with a p value Conclusion:We showed that positive RF was predictive of good clinical response to IV bDMARDs. For the first time, we demonstrated that number of US B-mode synovitis was also predictive to good clinical response.Disclosure of Interests:Stephane Giuliani Grant/research support from: BMS, Benjamin Laurent Grant/research support from: BMS, Hella MEZGHANI Employee of: BMS, Isabelle Duprat-Lomon Employee of: BMS, Amandine Luc Grant/research support from: BMS, Marcelo De carvalho Bittencourt Grant/research support from: BMS, Cedric BAUMANN Grant/research support from: BMS, Isabelle CHARY VALCKENAERE: None declared, Damien LOEUILLE: None declared

Alcohol is a potent agent for eliciting aggression in vertebrates. Taurine (TAU) is an amino sulfonic acid with pleiotropic actions on brain function. It is one of the most abundant molecules present in energy drinks frequently used as mixers for alcoholic beverages. However, the combined effects of TAU and ethanol (EtOH) on behavioral parameters such as aggression are poorly understood. Considering that zebrafish is a suitable vertebrate to assess agonistic behaviors using noninvasive protocols, we investigate whether TAU modulates EtOH-induced aggression in zebrafish using the mirror-induced aggression (MIA) test. Since body color can be altered by pharmacological agents and may be indicative of emotional state, we also evaluated the actions of EtOH and TAU on pigment response. Fish were acutely exposed to TAU (42, 150, and 400mg/L), EtOH (0.25%), or cotreated with both molecules for 1h and then placed in the test apparatus for 6min. EtOH, TAU 42, TAU 400, TAU 42/EtOH and TAU 400/EtOH showed increased aggression, while 150mg/L TAU only increased the latency to attack the mirror. This same concentration also prevented EtOH-induced aggression, suggesting that it antagonizes the effects of acute alcohol exposure. Representative ethograms revealed the existence of different aggressive patterns and our results were confirmed by an index used to estimate aggression in the MIA test. TAU did not alter pigment intensity, while EtOH and all cotreated groups presented a substantial increase in body color. Overall, these data show a biphasic effect of TAU on EtOH-induced aggression of zebrafish, which is not necessarily associated with changes in body color.

Taurine (TAU) is an amino sulfonic acid with several functions in central nervous system. Mounting evidence suggests that it acts in osmoregulation, neuromodulation and also as an inhibitory neurotransmitter. However, the effects of TAU on behavioral functions, especially on anxiety-related parameters, are limited. The adult zebrafish is a suitable model organism to examine anxiety-like behaviors since it presents neurotransmitter systems and behavioral functions evolutionary conserved. Anxiety in zebrafish can be measured by different tasks, analyzing the habituation to novelty, as well as the response to brightly lit environments. The aim of this study was to investigate whether acute TAU treatment alters anxiety-like behavior in zebrafish using the novel tank and the light-dark tests. Fish were individually treated with TAU (42, 150, and 400mg/L) for 1h and the behaviors were further analyzed for 6min in the novel tank or in the light-dark test. Control fish were handled in a similar manner, but kept only in home tank water. Although TAU did not alter locomotor and vertical activities, all concentrations significantly increased shuttling and time spent in lit compartment. Moreover, TAU 150 group showed a significant decrease in the number of risk assessment episodes. Overall, these data suggest that TAU exerts an anxiolytic-like effect in zebrafish and the comparative analysis of behavior using different tasks is an interesting strategy for neuropsychiatric studies related to anxiety in this species.

We investigate the behavioural responses of wild type (WT) and leopard (leo) zebrafish elicited by alarm substances of conspecifics at three contexts: during the exposure period (Experiment 1); after exposure, in habituation to novelty (Experiment 2); or after exposure, in the light-dark preference test (Experiment 3), and analyse their influence on pigment response. During the exposure, leo showed decreased vertical drifts, increased number and duration of erratic movements, while WT had increased erratic movements and latency to enter the top. In the novel tank, we observed that angular velocity decreased in WT exposed to alarm substance, which also presented increased fear responses. Contrastingly, leo increased the number of entries and time in top, indicating differences in habituation profile. Alarm substance increased the number of erratic movements in the light-dark test, but elicited different responses between strains in scototaxis, latency to enter the dark compartment and risk assessment episodes. Moreover, the body colour of zebrafish did not change after alarm substance exposure. Principal component analyses suggest that burst swimming, anxiety-like behaviours, and locomotion/exploration were the components that most accounted for total variances of Experiments 1, 2, and 3, respectively. We conclude that chemical cue from conspecifics triggers strain- and context-dependent responses.

Introduction Les biotherapies, recommandees par les societes savantes en seconde intention en cas d’echec du traitement conventionnel (csDMARDS), ont revolutionne depuis une vingtaine d’annee la prise en charge de la polyarthrite rhumatoide, ameliorant le pronostic vital et fonctionnel. Cependant, malgre un large arsenal therapeutique, il persiste une proportion significative de patients (environ 30 %) qui ne reponde pas au traitement. Objectifs Identifier des facteurs biologiques et d’imagerie (radiographie, echographie) predictifs de bonne reponse therapeutique aux biotherapies afin de cibler plus efficacement les patients a risque d’echec therapeutique et limiter les risques d’effets indesirables induits (infections, cancers induits, hemato toxicite). Patients et methodes De 2008 a 2017, les patients remplissant les criteres diagnostiques de polyarthrite rhumatoide et demarrant une biotherapie intraveineuse (rituximab, abatacept, infliximab, tocilizumab) ont ete selectionnes. Etait inclus les patients avec une maladie active (DAS28 > 3.2) et des donnees immunologiques (ACPA, FR) et d’imagerie (radiographiques et echographiques) disponibles. A six mois, la bonne reponse clinique etait definie par un DAS28 1.2 et la remission clinique par un DAS28 Resultats Cent cinquante-cinq patients ont ete inclus. Le DAS28 median etait de 5,3 (4,3–6,0), la mediane de biotherapies IV anterieures de 2,0 (1,0–3,0), la duree d’evolution etait de 11,5 annees, le score radiographique median d’erosion (SHS) de 36,5 (11,0–79,0). Parmi les patients, 85,2 % etaient ACPA+ et 74,5 % FR+. A 6 mois, 87 (56,1 %) et 33 (21,3 %) patients etaient respectivement en bonne reponse clinique et remission. En analyse multivariee, le statut FR+ et le nombre echographique de synovite en mode B etaient associees a une meilleure reponse clinique a 6 mois avec un odds ratio de 5,1 (IC95 % : 1,8–14,4) et 1,2 (IC95 % : 1,1–1,4) respectivement. Seul le nombre echographique de synovite en mode DP etait associe avec une remission clinique a 6 mois avec un odds ratio de 1,1 (IC95 % : 1,01–1,30). Discussion Le statut FR+ s’impose comme un facteur predictif de premier plan. Sa positivite confere 5 fois plus de chance d’etre repondeur au traitement biologique, au contraire du statut ACPA, de l’inflammation initiale evaluee par la CRP ou des facteurs cliniques (DAS28, duree d’evolution de la maladie, âge, sexe, nombre de biotherapie anterieure). Au niveau echographique, si le lien entre decroissance de l’inflammation echographique sous traitement est connu pour etre associe a une meilleure reponse therapeutique clinique a 6 mois, nous avons egalement montre que le nombre initial de synovite en mode B ou en mode DP est un facteur predictif independant de reponse. Pour autant, notre manque de puissance a limite une evaluation individuelle pour chaque biologique IV et cette etude ne saurait s’appliquer pour des biologiques par voie sous-cutanee ou pour les csDMARDS. De plus, une majorite presentait des polyarthrites anciennes en seconde ligne de biologique, ne permettant pas une extrapolation pour des polyarthrites recentes. Conclusion Le statut FR et le nombre initial de synovites (en mode B et DP) en echographie sont predictifs a 6 mois d’une meilleure reponse therapeutique aux biologiques IV chez les patients atteints de polyarthrite rhumatoide.

Background:RA is the most prevalent chronic inflammatory rheumatism, responsible of functional impairment.Objectives:To investigate the value of biological and imaging biomarkers on predicting DAS 28 remission at 6 months, in RA patients initiating IV bDMARD.Methods:From 2008 to 2017, 317 RA patients fulfilling ACR 1987 and/or ACR-EULAR 2010 criteria for RA, initiated IV bDMARDs in our department of Rheumatology. Patients were excluded in cases of lack of information on disease activity assessment before and at 6 months of treatment and on immunological status and titers (ACPA, RF, ANA) at baseline. For patients receiving successive IV bDMARDs during this time period (n=30), a randomization permitted to select 1 treatment sequence. On 173 patients eligible to the study, 4 were lost to follow-up and 14 stopped treatment due to adverse events before 6 months. Clinical, biological and imaging (US and RX) data, were collected when available at treatment initiation. US examination was performed on 12 targeted joints (wrist, MCP2-3-5 and MTP2-3-5) with qualitative and quantitative evaluation on B mode and Power Doppler (PD) for synovitis, tenosynovitis and erosion. The modified Sharp/van der Heijde erosion score was performed by 2 independent readers blindly from clinical and US informations. Remission was defined by a DAS 28 < 2.6 at 6 months. Only variables with a pTable 1.Characteristics of the patients (n=155) at baselineTable 2.Variables predictive of a DAS 28 remission at 6 months for IV bDMARDsBiomarkersUnivariateAnalysisBivariate Logistic regression AnalysisDAS 28 remission(n= 33)No Remission(n=122)p valueOR (CI95%)Clinical dataNb of sequence >119 (57.6%)92 (75.4%)0.0520.4 (0.2-1.0)Radiography (n=110)Erosive RA22 (88.0%)61 (71.8%)0.1180.3 (0.1-1.3)US (n=127)Erosive RA28 (96.6%)82 (83.7%)0.1170.2 (0.0-1.4)Nb B mode synovitis7.7 (4.5)5.5 (3.9)0.0130.9 (0.8-1.0)Nb PD+ synovitis6.5 (5.0)4.3 (3.3)0.0310.9 (0.8-1.0)All qualitative variables with a p value Results:On 155 RA patients, 11 had a disease duration < 2 year, 44 (28.3%) were on first line of IV bDMARDs and 111 patients received at least one IV bDMARD (mean 2.5 (1.3)).Conclusion:In RA patients treated by IV bDMARDs, number of PD+ synovitis on ultrasonography was the only predictive biomarker of DAS 28 remission.Disclosure of Interests:Benjamin Laurent Grant/research support from: BMS, Stephane Giuliani Grant/research support from: BMS, Hella MEZGHANI Employee of: BMS, Isabelle Duprat-Lomon Employee of: BMS, Amandine Luc Grant/research support from: BMS, Marcelo De carvalho Bittencourt Grant/research support from: BMS, Cedric BAUMANN Grant/research support from: BMS, Isabelle CHARY VALCKENAERE: None declared, Damien LOEUILLE: None declared

Radial joints are defined as the contact part between precast segments in each ring of mechanical excavated tunnel lining. The behavior of flat radial joints without connectors is investigated in this paper through full-scale experimental tests on fiber reinforced concrete elements without any traditional reinforcement. The tests were performed by imposing a joint opening, as typical can occur when higher level of ovalization in the lining are required. The results showed the effect of concrete crushing as well as the bursting phenomena. Finally, an analytical interpretation of the behavior is presented, providing useful information that can support the design of this type of joints.

Recent progress in inkjet printing of parts of biosensors are highlighted, with particular reference to the printing of biologically active molecules. We describe a system constituted by a thermal inkjet printer, adapted to layering a bidimensional array of dots [701 × 701 dots per inch] on solid supports. The printer was used to depose a β‐galactosidase (GAL)‐containing ink on a polyester sheet, with dots obtained from 10 pL drops, each drop containing in turn 6 pg of enzyme. The activity of GAL after the preparation was determined using a colorimetric probe (Brilliant Blue FCF). The activity loss of the microdeposed enzymes was found to be around 15%, showing that the 2 µsec‐lasting thermal shock experienced by the biomolecule into the printhead nozzle affects to a lesser extent the activity of the thermal inkjet deposited enzyme. In conclusion, the most recent findings of our group in this line are depicted, and a view of possible future developments of the “biopolytronics” field is outlined.

This paper presents a winter carbon budget for the northern Adriatic Sea, obtained through direct measurements during two multidisciplinary cruises and literature data. A box model approach was adopted to integrate estimates of stocks and fluxes of carbon species over the total area. The oligotrophy at the basin scale and the start of primary productivity well before the onset of spring stratification were observed. In winter, the system underwent a complete reset, as the mixing of water masses erased any signal of previous hypoxia or anoxia episodes. The northern Adriatic Sea was phosphorus depleted with respect to C and N availability. This fact confirms the importance of mixing with deep-sea water for P supply to biological processes on the whole. Despite the abundant prokaryotic biomass, the microbial food web was less efficient in organic C production than phytoplankton. In the upper layer, the carbon produced by primary production exceeded the fraction respired by planktonic community smaller than 200?m. On the contrary, respiration processes prevailed in the water column below the pycnocline. The carbon budget also proved that the northern Adriatic Sea can be an effective sink for atmospheric CO2 throughout the entire winter season.

The intestinal epithelial monolayer constitutes a physical and functional barrier between the organism and the external environment. It regulates nutrients absorption, water and ion fluxes, and represents the first defensive barrier against toxins and enteric pathogens. Epithelial cells are linked together at the apical junctional complex by tight junctions that reduce the extracellular space and the passage of charge entities while forming a physical barrier to lipophilic molecules. Cultured intestinal epithelial cells have been extensively used to study intestinal absorption of newly synthesized drugs and the regulation of tight junctions structure and function. In vitro mild irritants, proinflammatory cytokines, toxins and pathogens, and adverse environmental conditions open tight junctions and increase paracellular permeability, an effect often accompanied by immune activation of the enterocytes. Conversely, inhibition of proinflammatory cytokines, exposure to growth factors and probiotics, among others, exert a protective effect. Impaired barrier function results from activation of signalling pathways that lead to alteration of junctional proteins expression and/or distribution. In vivo, intestinal barrier dysfunction is associated with various intestinal and non-intestinal disorders including inflammatory bowel disease, celiac disease, and diarrhoeal infection. This review will describe the current knowledge of the mechanisms regulating tight junctions and intestinal permeability, how these findings have lead to a better understanding of barrier alteration in human intestinal disorders, and what the emerging therapies to treat these pathologies are.

Arylsulphatase A (ASA) activity was evaluated in 47 patients with a diagnosis of parkinsonism or essential tremor. Mean ASA activity was significantly reduced compared with both a healthy control group of 71 individuals (p < 0.01) and with a group of 44 neurological patients without movement disorders (p < 0.02). Using definite clinical criteria the patients were classified as typical or atypical with respect to Parkinson's disease (PD) or essential tremor (ET). A normal ASA level was found in all the cases showing typical clinical features (PD and ET), while ASA activity was significantly lowered (p < 0.01) in 55.6% of the atypical cases (Parkinsonian syndrome or symptomatic ET). Our data support the hypothesis of a non-casual association between low ASA level and the clinical features of parkinsonism or symptomatic ET.

A preliminary chemical and ecotoxicological assessment was performed on the produced formation water (PFW) and superficial sediment around a gas platform (Fratello Cluster), located in the Adriatic Sea (Italy), in order to evaluate the effects of PFW discharged from the installation. The ecotoxicological bioassays, with the marine bacterium Vibrio fischeri and the sea urchin Paracentrotus lividus, were associated with chemical data to estimate the possible effects on living organisms. PFW collected on the platform was toxic, but no significant effect was recorded on marine sediment. Only the sediment station nearest to the discharge point showed higher values of some contaminants (zinc and arsenic) in comparison to other sites and only some stations showed low toxicity.

The mucilage phenomenon has affected the Tuscan Archipelago since its first appearance (1991) in the Tyrrhenian Sea (Mediterranean Sea) [Innamorati M, Raddi E, Buzzichelli A, Melley S, Demoulin M. Le mucillaggini nel Mar Tirreno. Biol Mar Suppl Notiz 1992;1:23-26; Sartoni G, Sonni C. Tribonema marinum J. Feldmann e Acinetospora crinita (Carmichael) Sauvageau nelle formazioni mucillaginose bentoniche osservate sulle coste toscane nell'estate 1991. Inf Bot Ital 1991;23:23-30; Sartoni G, Cinelli F, Boddi S. Ruolo di Tribonema marinum J. Feldmann ed Acinetospora crinita (Carmichael) Sauvageau negli aggregati mucillaginosi bentonici delle coste toscane. Biol Mar Suppl Notiz 1993;1:31-34]. Seasonally, these mucous aggregates become very common in the benthic domain. The gorgonians are the most exposed organisms because they provide the best support for mucilage growth; indeed, their long branches positioned in orthogonally with respect to the current so as to capture plankton, also trap the filamentous mucilage present in the water. A 3-year monitoring programme at Capo Calvo (Island of Elba) was carried out in order to study the appearance of the mucilage phenomenon and its impact on three species of gorgonians (Eunicella cavolinii, Eunicella singularis, and Paramuricea clavata). The composition of mucilage and the gorgonian recovery capacity, when damaged, were investigated. During the first year of study (1999), no relevant interactions between gorgonians and mucilages were recorded. Instead, massive presence of mucilages causing different types of damage to the different gorgonian species investigated was recorded during the second (2000) and third year (2001). The type and the extent of the impact of mucilages also depend on the season. Three species of algae (Nematochrysopsis marina, Chrysonephos lewisii and Acinetospora crinita) constitute the principal components of the mucilaginous aggregates. In general, the first two species occur during the spring season, down to 20 m, while A. crinita occurs at greater depths. In July, when the mucilages reach their maximum development, C. lewisii is the predominant species. This species mainly affects E. cavolinii and E. singularis while A. crinita mainly affects P. clavata, which colonizes greater depths.

Pentylferulate synthesis was achieved at high yields (50–60%) with Aspergillus niger feruloyl esterase using a water-in-oil microemulsion system. The initial rate of synthesis decreased by 15–20% when the water content of the microemulsion was increased from 1.8 to 2.4% (v/v), although a concomitant decrease in conversion was not observed. The enzyme stability was significantly higher in the microemulsion than in an aqueous solution.

La linea progettuale, qui illustrata, è inserita nelle attività di uno dei laboratori a rete regionali chiamato LITCAR (Laboratorio Integrato Tecnologie e Controllo Ambientale nel ciclo di vita dei Rifiuti) finanziato tramite il PRRIITT della regione Emilia-Romagna. Il progetto si è occupato dello sviluppo e della realizzazione di inchiostri per stampa ink-jet a basso impatto ambientale che favoriscono il recupero della carta da macero ed il trattamento biologico delle acque reflue di disinchiostrazione. Tali inchiostri sono stati sviluppati attraverso le attività del laboratorio in collaborazione con ENEA di Bologna e vengono attualmente commercializzati con il nome di Ink-no-Ink dalla azienda Lesepidado srl (Bologna). Ink-no-Ink è stato classificato tra i primi 64 progetti innovativi segnalati da IlSole24ore nel volume Italian Applications del 2006. Lesepidado ha ricevuto nel 2007 il premio nazionale IMPRESA-AMBIENTE per la realizzazione di Ink-No-Ink

Eco-toxicology represents an important integrative tool of environmental risk assessment. Amphipods is a taxon much recommended for bioassay, but species used are generally from the Atlantic Ocean or the North Sea. None of the Mediterranean species has ever been examined. In an eco-toxicological evaluation of harbour sediment, Corophium orientale, an endemic Mediterranean species, was investigated for suitability to determine sediment quality. Physical-chemical analyses and amphipod bioassays on several contaminated Italian harbour samples were carried out. Two amphipod populations with different sensitivities were used. Microtox®, a sensitive and reproducible assay procedure, was used in parallel with C. orientale assay in order to ascertain an agreement and/or disagreement between responses. The results of the two bioassay procedures supported the hypothesis that C. orientale, as part of a battery of bioassays, is sensitive to hydro-soluble pollutants contaminating the water column due to dredging activities.

Nell’ottica di una Politica Integrata di Prodotto (IPP), abbiamo studiato il ciclo di vita di un inchiostro per stampa ink jet a carattere alimentare da utilizzare nell’office, al fine di ottenere un prodotto ecocompatibile in termini di riciclo di carta e cartucce esauste. Al termine dello studio è stato ottenuto un prodotto “ecologico” che riduce gli impatti ambientali del 68% rispetto ad un prodotto “tradizionale”. The aim of the research, in an Integrated Policy of Product, was to study the life cycle of a food suitable ink for ink-jet printing. This ink, used for office purpose, should be an environmental friendly product considering the paper and cartridges recycle. We produced an “ecological” product which reduces the environmental impacts of about 68% compared with “traditional” once.

L’impatto ambientale di un prodotto o di un processo è generalmente valutato utilizzando un approccio “from bottom to up” applicando un maggior controllo del danno ambientale del prodotto stesso durante il suo ciclo di vita. Tuttavia, la sostenibilità di un prodotto dovrebbe essere preventiva mettendo a punto un processo in grado di evitare il danno, applicando quindi cambiamenti sostanziali sia sul prodotto stesso che sul processo. L’eco-design è uno strumento fondamentale per lo sviluppo di tale approccio, in cui viene presa in considerazione ogni parte della realizzazione e dell’applicazione del prodotto, al fine di ottenerne uno nuovo, in accordo con il concetto di sostenibilità. In questo contesto si è inserito il seguente studio che ha portato allo sviluppo di un nuovo inchiostro per tecnologia inkjet ad uso ufficio a basso impatto ambientale tramite uno studio di eco-design di prodotto. Il ciclo di vita del prodotto ha tenuto conto delle tre principali linee di produzione che caratterizzano la carta stampata da ufficio: la produzione dell’inchiostro, la produzione delle cartucce e la produzione della carta compresivi dei loro eventuali recuperi e riusi. Da specifici studi di LCA (Life Cycle Assessment) di confronto si sono potuti individuare i punti critici sui quali realizzare un eco-design di prodotto che sono oggetto di questa comunicazione relativa ad una delle linee di ricerca del laboratorio a rete LITCAR nato nell’ambito del Programma Regionale per la Ricerca Industriale, l’Innovazione ed il Trasferimento Tecnologico, PRRIITT, (legge n. 7/2002) sulla base delle indicazioni contenute nel VI Programma Quadro per l’Ambiente. Lo studio qui descritto si inserisce in particolare nell’Obiettivo Realizzativo 4 “Inchiostri ecologici per tecnologia Ink-jet e piattaforme per il riciclo della carta da macero” della Linea Progettuale 1 “Prevenzione, tramite innovazione dei processi, per la riduzione di quantità e pericolosità dei rifiuti”.

[Objective] The aim of this study was to determine in intact and inflamed knee joints of the rat, the effect of the bradykinin (BK) B2 receptor antagonist fasitibant (MEN16132) on nociceptor mechanosensitivity and hyperalgesia., [Methods] Joint afferent sensory fibers of the medial articular nerve of anesthetized animals were electrophysiologically recorded, measuring nerve impulse activity evoked by passive innocuous and noxious movements of the joint, in intact and kaolin and carrageenan-injected joints. Knee joints of rats were also acutely inflamed by intra-articular injection of carrageenan alone. Long term duration of fasitibant antinociceptive effects were behaviorally evaluated using the incapacitance test., [Results] BK (100 μM) injected into the saphenous artery, induced excitation and sensitization of multi- and single unit recordings. Fasitibant (300 μM) injected prior to BK, reduced its excitatory effects as well as the overall increase of movement-evoked activity resulting from repeated injections of BK. Fasitibant did not affect movement-evoked activity of sensory fibers of intact, non-inflamed knee joints. Intra-articular fasitibant (100 μg/knee) significantly reduced the carrageenan-induced inflammatory hyperalgesia measured with the incapacitance test up to four days after treatment. This antinociceptive effect was not obtained with systemic endovenous injection of the drug., [Conclusions] Fasitibant prevents B2 receptor-mediated activation and sensitization of peripheral joint afferents and the ensuing inflammatory hyperalgesia, and may be a useful, novel drug for arthritis pain treatment., This work was supported by grants from Spanish MICINN BFU2009-07835 to AG, BFU2008-04425 to CB and CONSOLIDER-INGENIO 2010 CSD2007-00023.

1. The aim of this study was to assess the role of tachykinins, acting via NK1 and NK2 receptors, in mediating nonadrenergic noncholinergic (NANC) contractions produced by electrical field stimulation (EFS) in the circular muscle of the rat small intestine. 2. In the presence of atropine (1 microM), guanethidine (3 microM), indomethacin (10 microM), apamin (0.3 microM) and L-nitroarginine (L-NOARG, 100 microM) and after in vitro capsaicin (10 microM for 15 min) pretreatment, EFS (0.25 ms pulse width, 100 V, 1-30 Hz for 5 s) produced a frequency-dependent NANC contraction of mucosa-free circular muscle strips from the rat proximal duodenum and terminal ileum. In the duodenum, the NANC contraction was preceded by a transient NANC relaxation. All responses to EFS were abolished by 1 microM tetrodotoxin. 3. The NK1 receptor selective antagonist, SR 140,333 (0.1 microM for 60 min) and the NK2 receptor selective antagonist, MEN 10,627 (0.1 microM for 60 min), both produced a partial inhibition of the contractile response to EFS. The co-administration of SR 140,333 and MEN 10,627 produced a profound inhibition of the response to EFS in the duodenum, larger than that produced by each antagonist alone; a fraction (about 25% of the response at 30 Hz) of the NANC contraction of the duodenum persisted in the presence of the two antagonists. This residual response was however abolished after co-administration of the NK1 and NK2 receptor antagonists, GR 94,800 (1 microM) and GR 82,334 (10 microM). The co-administration of SR 140,333 and MEN 10,627 nearly abolished the NANC contraction to EFS in the ileum. 4. Nifedipine (1 microM) induced a profound depression of the NANC contraction to EFS in both duodenal and ileal strips. A fraction of the response to EFS (about 25 and 5-10% of the response at 30 Hz in the duodenum and ileum, respectively) was nifedipine-resistant. SR 140,333 (0.1 microM) had little effect on the nifedipine-resistant response to EFS in the duodenum although it reduced by about 50% the response in the ileum. MEN 10,627 (0.1 microM) produced a partial inhibitory effect of the nifedipine-resistant response in both regions. The co-administration of SR 140,333 and MEN 10,627 nearly abolished the nifedipine-resistant response in the ileum while a small fraction (about 20% of control) of the response persisted in the duodenum.

1 Measurement of plasma protein extravasation induced by the natural tachykinins following intradermal administration in rat skin indicated equipotency between substance P (SP), neurokinin A (NKA) and neurokinin B (NKB). The selective NK1 receptor agonist, [Sar9]SP sulphone was 10–100 times more potent than SP. The synthetic hexapeptide, septide, [pGlu6, Pro9]SP-(6–11), which has been proposed to act on a distinct NK1 receptor subtype/binding site was equipotent with [Sar9]SP sulphone. 2 The selective NK2 receptor agonist [βA1a8]NKA(4–10) (0.1-1 nmol) and the selective NK3 receptor agonist, senktide (0.1-1 nmol) were both ineffective in producing oedema. The selective NK2 receptor antagonist, SR 48, 968 (0.3 μmol kg−1) had no significant inhibitory effects upon oedema induced by approximately equiactive doses of SP (0.2 nmol), septide (0.002 nmol), [Sar9]SP sulphone (0.002 nmol), or NKB (0.3 nmol). These results together suggest that neither NK2 nor NK3 receptors are involved in oedema formation in rat skin. 3 The non-peptide tachykinin NK1 receptor antagonist, RP 67, 580 (1–3 μmol kg−1), inhibited plasma protein extravasation induced by septide (0.002 nmol) to a greater extent than that to SP (0.2 nmol). RP 67, 580 (1 μmol kg−1) produced a significant inhibition of approximately 66% of the response to septide (0.002 nmol) only. Increasing the dose of RP 67, 580 3 fold resulted in inhibition of the response to SP (0.2 nmol) and [Sar9]SP sulphone (0.002 nmol) by approximately 66% and 64% respectively with the response to septide being inhibited by approximately 70%. 4 Co-administration of the nitric oxide (NO) synthase inhibitor, NG-nitro-L-arginine methyl ester (L-NAME) (0.1 μmol) with the relevant tachykinin, resulted in a significant attenuation of the oedema response to septide (0.1 nmol) producing only an approximate 56% inhibition of the response. The response to 0.2 nmol SP was unaffected whereas the response to a higher dose of 1 nmol was lowered by L-NAME but this did not reach significance. 5 Degranulation of mast cells, achieved by pretreatment with compound 48/80 (5 mg kg−1) for 3 consecutive days, significantly inhibited the oedema responses to only high dose SP (1 nmol) and [Sar9]SP sulphone (0.002 nmol). SP (0.2 nmol), septide (0.002 nmol), NKA (0.2 nmol) and NKB (0.3 nmol) were unaffected by this treatment. 6 RP 67, 580 (0.3-3 μmol kg−1) inhibited oedema induced by both 0.002 nmol and 0.1 nmol of septide. When using equiactive doses of SP only the response to the lower dose of 0.2 nmol SP was significantly inhibited, while RP 67, 580 (3 1μmol kg−1) did not affect the response to 1 nmol SP. 7 These results suggest distinct mechanisms of action for SP and septide in producing plasma protein extravasation in rat skin. The response induced by septide is blocked by RP 67, 580 and is both NO-dependent and mast-cell independent. In contrast the response to SP is only partially blocked by RP 67, 580 and is NO-independent. These data support the existence of a distinct ‘septide-sensitive’ receptor/ binding site and suggest that this site is involved in tachykinin-induced oedema formation in rat skin.

Triple negative breast carcinomas (TNT) are infiltrating breast carcinomas (BC) with negative oestrogen receptor (ER), progesterone receptor (PgR) and human epidermal growth factor receptor 2 (HER-2) expression, and are associated with frequent BRCA1/BRCA2 mutations. The aim of the present study is to analyze the frequency and distribution of TNT in our population where a breast cancer screening program for women aged between 50 and 69 years is effective since 2001 with 85% accrual.We investigated the records of 2112 consecutive BC and 153 interval BC (i.e. BC detected in the screened negative women in the interval between screening rounds). Tumours with complete negative expression of ER, PgR and Her2 were considered TNT; tumours with negative ER and PgR status and faint Her2 expression (score 1) were considered as possible TNT (pTNT).We identified 82 (3.8%) TNT and 20 (0.9%) pTNT in the series of 2112 consecutive BC and 7 TNT and 1 pTNT (5.2%) in the series of 153 interval BC. In the consecutive series, TNT/ pTNT were observed in 6.5% patients below 50 years and in 4.3% of patients above 50 years. A high proliferation rate (Ki-67 labelling36%) was observed in 87.8% of TNT (median labelling 56.3%) and in 60% of pTNT (median labelling 48.4%).Since TNT/pTNT occurring in women50 years is a criterion for selecting patients whom genetic counselling and BRCA1 testing should be offered, our study is of help in foreseeing the workload of the Unit of Medical Genetics and the Laboratory of Molecular Pathology.

Climate has been acknowledged as one of the main driving factors behind human development and in turn human activity may cause strong changes on marine ecosystems. Coastal areas represent very useful marine sedimentary archives to investigate the potential effects of human impact on shelf marine ecosystems. The high-resolution investigation presented here of a southern Tyrrhenian marine record from the continental shelf of the Salerno Gulf provides an unprecedented opportunity to study the main natural and human impact that have occurred in this area during the last five centuries. Evidence of an important turnover between carnivorous and herbivorous opportunistic planktonic foraminfera species is recorded after the Maunder event. In addition, after 1940 AD, a strong increase in the distribution pattern of the Globigerina bulloides species combined with a sudden increase in the abundance pattern of the benthic foraminifer Bulimina aculeata, and evident enhancement of benthic and planktonic foraminifera (as number of specimens per gram of dry sediment) can be directly associated to the effects of the construction of the Sele River dam (1934 AD).

Climate has been acknowledged as one of the main driving factors behind human development and in turn human activity may cause strong changes on marine ecosystems. Coastal areas represent very useful marine sedimentary archives to investigate the potential effects of human impact on shelf marine ecosystems. The high-resolution investigation presented here of a southern Tyrrhenian marine record from the continental shelf of the Salerno Gulf provides an unprecedented opportunity to study the main natural and human impact that have occurred in this area during the last five centuries. Evidence of an important turnover between carnivorous and herbivorous opportunistic planktonic foraminfera species is recorded after the Maunder event. In addition, after 1940 AD, a strong increase in the distribution pattern of the Globigerina bulloides species combined with a sudden increase in the abundance pattern of the benthic foraminifer Bulimina aculeata, and evident enhancement of benthic and planktonic foraminifera (as number of specimens per gram of dry sediment) can be directly associated to the effects of the construction of the Sele River dam (1934 AD).

In osteoarthritis (OA), bradykinin (BK) is known to contribute to pain and synovitis, but not to cartilage degradation. Here, we investigated effects of BK and its antagonists on chondrocytes, cells involved in cartilage homeostasis.BK receptor density and affinities of BK, its analogues and antagonists were measured in cultured human and rat chondrocytes by radioligand binding. Effects of BK were assessed by accumulation of inositol phosphates (IP) and release of interleukin (IL)-6 and IL-8.Density of [³H]-BK binding sites was higher (13-30-fold) and BK evoked a greater (48-fold) IP production, in human than in rat chondrocytes. The BK B₂ receptor antagonists MEN16132 and icatibant displayed similar binding affinity. MEN16132 was 40-fold more potent than icatibant in the IP assay. In human chondrocytes, BK increased release (over 24 h) of IL-6 and IL-8, effects blocked by MEN16132 but not by the B₁ receptor antagonist Lys-[Leu⁸][desArg⁹]BK. BK-induced release of IL-6, but not of IL-8, was partially inhibited by indomethacin (10 µM) and nordihydroguaiaretic acid (10 µM). Antagonists for the prostanoid EP receptors (AH6809 10 µM; L-798,196, 200 nM; L-161,982, 1 µM) were ineffective. Dexamethasone (100 nM) partially inhibited release of both IL-6 and IL-8. Inhibitors of intracellular downstream signalling pathways (SB203580 10 µM; PD98059, 30 µM; SP600125, 30 µM; BAY-117085, 5 µM) indicated the involvement of p38 MAPK and the activation of NF-κB.BK mediated inflammatory changes and cartilage degradation and B₂ receptor blockade would, therefore, be a potential treatment for OA.

Bradykinin (BK) and B2 receptors have been implicated in the pathophysiology of osteoarthritis (OA), and synovitis is one of its hallmarks. Here, the selective B2 receptor antagonists MEN16132 and icatibant have been pharmacologically characterized in human synovial cells.Radioligand and functional studies (inositol phosphate (IP) accumulation, interleukin (IL)-6 and IL-8 release) were performed in cultured synoviocytes.[3H]-BK saturation studies indicated receptor density (Bmax) and K(d) values of 121,550 sites per cell and 1.14 nM respectively. In synoviocytes, MEN16132 (pK(I) 8.9) was threefold more potent than icatibant (pK(I) 8.4). Both antagonists showed competitive antagonism in the BK-induced IP assay (control EC50 0.45 nM), with pK(B) values of 9.9 (MEN16132) and 8.1 (icatibant). 24h incubation with BK induced IL-6 (EC50 216 nM) and IL-8 (EC50 53 nM) release. Both MEN16132 (IL-6: pIC50 8.1; IL-8: pIC50 8.4) and icatibant (IL-6: pIC50 6.6; IL-8: pIC50 6.7) completely prevented this BK-induced release. Indomethacin did not affect the basal or the IL-6/IL-8 release induced by BK, whereas nordihydroguaiaretic acid decreased the basal release, although BK still increased IL-6 and IL-8 production. BK-induced IL-8 release was attenuated by inhibitors of phospholipase C (U73122), p38 (SB203580), JNK (SP600125), ERK 1/2 (PD98059) MAPKs, phosphoinositide 3-kinase (LY294002), NF-kappaB (BAY-117085) and by the glucocorticoid dexamethasone.Bradykinin via B2 receptors can participate in inflammatory events in synovitis. MEN16132 is a highly potent B2 receptor antagonist capable of blocking pro-inflammatory responses to BK evoked in human synoviocytes.

Four cases of hemifacial spasm (HFS) are reported. The spasm followed a few months after injury to a peripheral branch of the seventh nerve. An EMG examination of facial muscles disclosed the typical finding of HFS: spontaneous activity, paradoxical cocontraction, and diffusion of spontaneous or provoked blinking. A nuclear involvement, secondary to the nerve lesion, is the most likely pathophysiological explanation for similar cases in HFS.