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Search Results: 1 - 10 of 22380 matches for " Roberto Ciccocioppo "
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MT-7716, a novel selective nonpeptidergic NOP receptor agonist, effectively blocks ethanol-induced increase in GABAergic transmission in the rat central amygdala
Marsida Kallupi,Christopher S. Oleata,Koji Teshima,Roberto Ciccocioppo,Marisa Roberto
Frontiers in Integrative Neuroscience , 2014, DOI: 10.3389/fnint.2014.00018
Abstract: The GABAergic system in the central amygdala (CeA) plays a major role in ethanol dependence and the anxiogenic-like response to ethanol withdrawal. A large body of evidence shows that Nociceptin/Orphanin FQ (N/OFQ) regulates ethanol intake and anxiety-like behavior. In the rat, ethanol significantly augments CeA GABA release, whereas N/OFQ diminishes it. Using electrophysiological techniques in an in vitro slice preparation, in this study we investigated the effects of a nonpeptidergic NOP receptor agonist, MT-7716 [(R)-2-3-[1-(Acenaphthen-1-yl)piperidin-4-yl]-2-oxo-2,3-dihydro-1H-benzimidazol-1-yl-N-methylacetamide hydrochloride hydrate], and its interaction with ethanol on GABAergic transmission in CeA slices of na?ve rats. We found that MT-7716 dose-dependently (100–1000 nM) diminished evoked GABAA receptor-mediated inhibitory postsynaptic potentials (IPSPs) and increased paired-pulse facilitation (PPF) ratio of these evoked IPSPs, suggesting a presynaptic site of action of the MT-7716 by decreasing GABA release at CeA synapses. The presynaptic action of MT-7716 was also supported by the significant decrease in the frequency of miniature inhibitory postsynaptic currents (mIPSCs) induced by the nociceptin receptor (NOP) agonist. Interestingly, MT-7716 prevented the ethanol-induced augmentation of evoked IPSPs. A putative selective NOP antagonist, [Nphe1]Nociceptin(1–13)NH2, totally prevented the MT-7716-induced inhibition of IPSP amplitudes indicating that MT-7716 exerts its effect through NOPs. These data provide support for an interaction between the nociceptin and GABAergic systems in the CeA and for the anti-alcohol properties of the NOP activation. The development of a synthetic nonpeptidergic NOP receptor agonist such as MT-7716 may represent a useful therapeutic target for alcoholism.
Comparative Oral Absorption of Different Citicoline and Homotaurine Formulations: A Single-Dose, Two-Period Crossover Trial in the Dog  [PDF]
Andrea Marchegiani, Ferdinando Nicoletti, Maria Rosaria Romano, Decio Capobianco, Ciro Costagliola, Carlotta Marini, Giuseppe Lubrano Lavadera, Roberto Ciccocioppo, Andrea Spaterna
Journal of Biomedical Science and Engineering (JBiSE) , 2019, DOI: 10.4236/jbise.2019.127028
Abstract: Background: Citicoline and homotaurine are compounds with a potent neuroprotective activity and they have been administered for many years in the treatment of numerous neurodegenerative and ophthalmological diseases, including glaucoma. Initially available only as liquid form, through parenteral route, nowadays citicoline can be administered also as tablet but no data on bioavailability of these different forms are available. In the present study, pharmacokinetics of citicoline in tablet versus vials, each at the therapeutic dose of 500 mg, in addition to 50 mg of homotaurine was investigated. Materials and methods: Ten mixed breed dogs received a single dose of 50 mg oral homotaurine and 500 mg citicoline in tablet and vials with the same dose were administered after a seven days wash-out period. Parameters assessed for citicoline metabolites (cytidine, uridine and choline) were AUC0t, Cmax and Tmax. Results: Citicoline bioavailability appeared to be slightly higher for the tablet compared to the vial formulation. Cytidine is equivalent in absorption dynamics both for tablet and liquid form; uridine for tablet reaches its maximum and is reabsorbed more quickly while choline for the liquid form reaches the maximum first and is reabsorbed more quickly. Conclusions: Citicoline in tablet and liquid formulation have pharmacokinetic properties leading to a very similar bioavailability.
Role of a Genetic Polymorphism in the Corticotropin-Releasing Factor Receptor 1 Gene in Alcohol Drinking and Seeking Behaviors of Marchigian Sardinian Alcohol-Preferring Rats
Lydia O. Ayanwuyi,Francisca Carvajal,Jose M. Lerma-Cabrera,Esi Domi,Karl Bj?rk,Massimo Ubaldi,Markus Heilig,Marisa Roberto,Roberto Ciccocioppo,Andrea Cippitelli
Frontiers in Psychiatry , 2013, DOI: 10.3389/fpsyt.2013.00023
Abstract: Marchigian Sardinian alcohol-preferring (msP) rats exhibit innate preference for alcohol, are highly sensitive to stress and stress-induced alcohol seeking. Genetic analysis showed that over-expression of the corticotropin-releasing factor (CRF) system of msP rats is correlated with the presence of two single nucleotide polymorphisms (SNPs) occurring in the promoter region (position ?1836 and ?2097) of the CRF1 receptor (CRF1-R) gene. Here we examined whether these point mutations were associated to the innate alcohol preference, stress-induced drinking, and seeking. We have recently re-derived the msP rats to obtain two distinct lines carrying the wild type (GG) and the point mutations (AA), respectively. The phenotypic characteristics of these two lines were compared with those of unselected Wistar rats. Both AA and GG rats showed similar patterns of voluntary alcohol intake and preference. Similarly, the pharmacological stressor yohimbine (0.0, 0.625, 1.25, and 2.5 mg/kg) elicited increased operant alcohol self-administration under fixed and progressive ratio reinforcement schedules in all three lines. Following extinction, yohimbine (0.0, 0.625, 1.25, and 2.5 mg/kg) significantly reinstated alcohol seeking in the three groups. However, at the highest dose this effect was no longer evident in AA rats. Treatment with the CRF1-R antagonist antalarmin (0, 5, 10, and 20 mg/kg) significantly reduced alcohol-reinforced lever pressing in the AA line (10 and 20 mg/kg) while a weaker or no effect was observed in the Wistar and the GG group, respectively. Finally, antalarmin significantly reduced yohimbine-induced increase in alcohol drinking in all three groups. In conclusion, these specific SNPs in the CRF1-R gene do not seem to play a primary role in the expression of the msP excessive drinking phenotype or stress-induced drinking but may be associated with a decreased threshold for stress-induced alcohol seeking and an increased sensitivity to the effects of pharmacological blockade of CRF1-R on alcohol drinking.
Endocannabinoid Regulation of Acute and Protracted Nicotine Withdrawal: Effect of FAAH Inhibition
Andrea Cippitelli, Giuseppe Astarita, Andrea Duranti, Giovanni Caprioli, Massimo Ubaldi, Serena Stopponi, Marsida Kallupi, Gianni Sagratini, Fernando Rodrìguez de Fonseca, Daniele Piomelli, Roberto Ciccocioppo
PLOS ONE , 2011, DOI: 10.1371/journal.pone.0028142
Abstract: Evidence shows that the endocannabinoid system modulates the addictive properties of nicotine. In the present study, we hypothesized that spontaneous withdrawal resulting from removal of chronically implanted transdermal nicotine patches is regulated by the endocannabinoid system. A 7-day nicotine dependence procedure (5.2 mg/rat/day) elicited occurrence of reliable nicotine abstinence symptoms in Wistar rats. Somatic and affective withdrawal signs were observed at 16 and 34 hours following removal of nicotine patches, respectively. Further behavioral manifestations including decrease in locomotor activity and increased weight gain also occurred during withdrawal. Expression of spontaneous nicotine withdrawal was accompanied by fluctuation in levels of the endocannabinoid anandamide (AEA) in several brain structures including the amygdala, the hippocampus, the hypothalamus and the prefrontal cortex. Conversely, levels of 2-arachidonoyl-sn-glycerol were not significantly altered. Pharmacological inhibition of fatty acid amide hydrolase (FAAH), the enzyme responsible for the intracellular degradation of AEA, by URB597 (0.1 and 0.3 mg/kg, i.p.), reduced withdrawal-induced anxiety as assessed by the elevated plus maze test and the shock-probe defensive burying paradigm, but did not prevent the occurrence of somatic signs. Together, the results indicate that pharmacological strategies aimed at enhancing endocannabinoid signaling may offer therapeutic advantages to treat the negative affective state produced by nicotine withdrawal, which is critical for the maintenance of tobacco use.
Therapeutic application of stem cells in gastroenterology: An up-date
Patrizia Burra,Debora Bizzaro,Rachele Ciccocioppo,Fabio Marra
World Journal of Gastroenterology , 2011, DOI: 10.3748/wjg.v17.i34.3870
Abstract: Adult stem cells represent the self-renewing progenitors of numerous body tissues, and they are currently classified according to their origin and differentiation ability. In recent years, the research on stem cells has expanded enormously and holds therapeutic promises for many patients suffering from currently disabling diseases. This paper focuses on the possible use of stem cells in the two main clinical settings in gastroenterology, i.e., hepatic and intestinal diseases, which have a strong impact on public health worldwide. Despite encouraging results obtained in both regenerative medicine and immune-mediated conditions, further studies are needed to fully understand the biology of stem cells and carefully assess their putative oncogenic properties. Moreover, the research on stem cells arouses fervent ethical, social and political debate. The Italian Society of Gastroenterology sponsored a workshop on stem cells held in Verona during the XVI Congress of the Federation of Italian Societies of Digestive Diseases (March 6-9, 2010). Here, we report on the issues discussed, including liver and intestinal diseases that may benefit from stem cell therapy, the biology of hepatic and intestinal tissue repair, and stem cell usage in clinical trials.
The tumor suppressor gene KCTD11REN is regulated by Sp1 and methylation and its expression is reduced in tumors
M Michela Mancarelli, Francesca Zazzeroni, Lucia Ciccocioppo, Daria Capece, Agnese Po, Simona Murgo, Raffaello Di Camillo, Christian Rinaldi, Elisabetta Ferretti, Alberto Gulino, Edoardo Alesse
Molecular Cancer , 2010, DOI: 10.1186/1476-4598-9-172
Abstract: TSGs often locate at chromosomal regions, which are frequently deleted and/or methylated in tumors. High levels of 17p13 somatic alterations have been showed in several tumors, distal and independent of the p53 locus [1-4].Our group has identified KCTD11 as an immediate-early gene induced by neurogenic signals [5] and encoding a novel adaptor of Cullin3 ubiquitin E3 ligase complex targeting Histone Deacetylase 1 [6]. Importantly, KCTD11 is a novel TSG that inhibits cell growth and is mapping on human chromosome 17p13.2, whose expression is frequently lost in human MB [4].To analyze whether the down-regulation of KCTD11 represents a specific feature of MB, as well to other cancers, we performed a wide screening for KCTD11 expression, analyzing 177 human tumor samples and 177 normal matching samples, representing 18 different cancer types. Normal tissues, including larynx, esophagus, stomach, colon-rectum, urinary bladder, lung, breast, gallbladder and endometrium, exhibited a nuclear KCTD11 positive immunohistochemical staining between 40 to 78% (Fig. 1B), whereas the matching tumor samples showed a significant reduction of 0 to 18% of nuclear KCTD11 staining (Fig. 1A and 1B). Reduced KCTD11 expression was not observed in thyroid and kidney tumor tissues vs normal suggesting a tumorigenic specific role of KCTD11 for the above mentioned tissues (Fig. 1A and 1B and data not shown). Moreover KCTD11 was undetected both in normal and cancer tissues from liver, lymph-node and exocrine pancreas (data not shown). Together, these findings clearly indicated that selective tissues expressing KCTD11 have down-regulated this gene during tumorigenesis.To understand the transcriptional regulation of KCTD11, we identified and analyzed the promoter region. Human KCTD11 proximal promoter is a 623 bp region (Fig. 2A). It turned out to be a TATA- and CAAT-less promoter. The transcription start site (TSS) was previously identified [4] (Fig. 2A). Using the TRANSFACT software, we identifie
Prognostic Value of HPV E6/E7 mRNA Assay in Women with Negative Colposcopy or CIN1 Histology Result: A Follow-Up Study
Paolo Giorgi Rossi, Maria Benevolo, Amina Vocaturo, Donatella Caraceni, Lucia Ciccocioppo, Antonio Frega, Irene Terrenato, Roberta Zappacosta, Deborah French, Sandra Rosini
PLOS ONE , 2013, DOI: 10.1371/journal.pone.0057600
Abstract: Pap test, and especially HPV DNA test, identify a large group of women who do not have any clinically relevant lesions, i.e., CIN2+ (Cervical Intraepithelial Neoplasia grade 2 or worse), but who are at greater risk of getting lesions in the future. The follow up of these women needs new biomarkers with prognostic value. The objective of this study is to evaluate the prognostic value of E6/E7 mRNA over-expression assay (PreTect HPV-Proofer, Norchip) for 5 HR-HPV types (16, 18, 31, 33, and 45) for progression to CIN2+ after a negative colposcopy. This prospective study, conducted at four Italian centres, enrolled 673 women with either a negative colposcopy or a negative or CIN1 histology. The clinical end-point was histological confirmation of CIN2+. Women were classified at baseline according to mRNA results and managed according to local colposcopy protocols. At least one conclusive follow-up test was obtained for 347 women (25 months average lapse since recruitment, range 5–74). Only seven CIN2+ were detected during follow up, three among the 82 women positive for mRNA at baseline, two among the 250 negative (Fisher exact test, p = 0.02), and two among the 12 with an invalid test. Absolute CIN2+ risk was 6.7/1,000 person/years in the whole cohort. The absolute CIN2+ risk was 18.4/1,000 person/years and 3.6/1,000 person/years in mRNA-positive and mRNA-negative women, respectively. In conclusion, E6/E7 mRNA over-expression appears to be a good candidate as a prognostic biomarker to manage HR-HPV DNA-positive women with negative colposcopy or histology, particularly in order to decrease follow-up intensity in those who are negative.
Integer Programming Formulations for Maximum Lifetime Broadcasting Problems in Wireless Sensor Networks  [PDF]
Roberto Montemanni
Wireless Sensor Network (WSN) , 2010, DOI: 10.4236/wsn.2010.212111
Abstract: Approaches based on integer linear programming have been recently proposed for topology optimization in wireless sensor networks. They are, however, based on over-theoretical, unrealistic models. Our aim is to show that it is possible to accommodate realistic models for energy consumption and communication protocols into integer linear programming. We analyze the maximum lifetime broadcasting topology problem and we present realistic models that are also shown to provide efficient and practical solving tools. We present a strategy to substantially speed up the convergence of the solving process of our algorithm. This strategy introduces a practical drawback, however, in the characteristics of the optimal solutions retrieved. A method to overcome this drawback is discussed. Computational experiments are reported.
Innovation in the Financial Sector: Persistence and Schumpeterian Hypotheses  [PDF]
Roberto Napoli
Journal of Service Science and Management (JSSM) , 2008, DOI: 10.4236/jssm.2008.13023
Abstract: The paper analyses innovation features in the German financial sector. The first topic is persistence of innovation. Our research question is: Do innovators plan further innovation for the subsequent year? In addition, since the sector is so far poorly researched, very basic questions are investigated in the paper: the relationship between firm size and innovation (both linear and quadratic), as well as the impact of market structure on innovation (i.e. Schumpeterian and neo-Schumpeterian hypotheses). Finally, Suttons argument of R & D sunk costs is investigated as a possible explanation for persistence. Basing on the CIS IV survey, our empirical evidence is consistent with the results of similar researches carried out in different sectors.
Development, Poverty and Energy, in the 21st Century  [PDF]
Roberto Kozulj
Modern Economy (ME) , 2011, DOI: 10.4236/me.2011.24054
Abstract: This work explores the area of global interdependences and the global context. In particular it deals with interdependences that seem to be absent from current literature but could be of great significance to identify the biggest challenges that the economy and the energy sector will have to face in the next two or three decades. In that sense, several issues are addressed: the dynamics of economic growth and its future; the relation between these dynamics and the foreseeable importance that urban poverty is to have at a global scale; the lack and inadequacy of information to approach crucial interdependences; and the need for a change in institutions and thinking habits to analyze the future. The approach focuses on the complex relationships that link urbanization, development phases, and technological changes dependent on products with shorter life cycles, discussing the impact of this kind of process over the genesis of urban poverty and over the structural modifications of economy. At the same time, a view on how these interdependences will become a serious and increasingly complex challenge for the energy sector and long term global sustainability is presented. The author also emphasizes the fact that these interdependences will become a serious and increasingly complex challenge that the energy sector will have to face if long term sustainability is to be attained.
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