Ruperto N.,IRCCS G Gaslini |
Carozzino L.,Local Health Unit Azienda Sanitaria Locale ASL 3 Genovese |
Jamone R.,Local Health Unit Azienda Sanitaria Locale ASL 3 Genovese |
Freschi F.,Local Health Unit Azienda Sanitaria Locale ASL 3 Genovese |
And 7 more authors.
Italian Journal of Pediatrics | Year: 2011
Background: To evaluate the analgesic effect and tolerability of paracetamol syrup compared to placebo and ketoprofen lysine salt in children with pharyngotonsillitis cared by family pediatricians. Methods. A double-blind, randomized, placebo-controlled trial of a 12 mg/kg single dose of paracetamol paralleled by open-label ketoprofren lysine salt sachet 40 mg. Six to 12 years old children with diagnosis of pharyngo-tonsillitis and a Children's Sore Throat Pain (CSTP) Thermometer score > 120 mm were enrolled. Primary endpoint was the Sum of Pain Intensity Differences (SPID) of the CSTP Intensity scale by the child. Results: 97 children were equally randomized to paracetamol, placebo or ketoprofen. Paracetamol was significantly more effective than placebo in the SPID of children and parents (P < 0.05) but not in the SPID reported by investigators, 1 hour after drug administration. Global evaluation of efficacy showed a statistically significant advantage of paracetamol over placebo after 1 hour either for children, parents or investigators. Patients treated in open fashion with ketoprofen lysine salt, showed similar improvement in pain over time. All treatments were well-tolerated. Conclusions: A single oral dose of paracetamol or ketoprofen lysine salt are safe and effective analgesic treatments for children with sore throat in daily pediatric ambulatory care. © 2011 Ruperto et al; licensee BioMed Central Ltd.
Blandino A.,University of Perugia |
Blandino A.,Acraf S.p.A. |
Lico C.,ENEA |
Baschieri S.,ENEA |
And 4 more authors.
Colloids and Surfaces B: Biointerfaces | Year: 2015
The use of biological self-assembling materials, plant virus nanoparticles in particular, appears very intriguing as it allows a great choice of symmetries and dimensions, easy chemical and biological engineering of both surface and/or internal cavity as well as safe and rapid production in plants. In this perspective, we present an initial evaluation of the safety profile of two structurally different plant viruses produced in Nicotiana benthamiana L. plants: the filamentous Potato virus X and the icosahedral Tomato bushy stunt virus. In vitro haemolysis assay was used to test the cytotoxic effects, which could arise by pVNPs interaction with cellular membranes, while early embryo assay was used to evaluate toxicity and teratogenicity in vivo. Data indicates that these structurally robust particles, still able to infect plants after incubation in serum up to 24. h, have neither toxic nor teratogenic effects in vitro and in vivo. This work represents the first safety-focused characterization of pVNPs in view of their possible use as drug delivery carriers. © 2015 Elsevier B.V.
Blasi F.,University of Milan |
Schaberg T.,Zentrum fur Pneumologie |
Centanni S.,University of Milan |
Del Vecchio A.,ACRAF SpA |
And 2 more authors.
Pulmonary Pharmacology and Therapeutics | Year: 2013
Rationale: Antimicrobial therapy of chronic bronchitis exacerbations in patients with severe chronic obstructive pulmonary disease (COPD) is based on empiric antibiotic treatment. Objectives: To evaluate the efficacy of prulifloxacin versus levofloxacin therapy in severe COPD patients with exacerbations of chronic bronchitis. Methods: This study involved a multicenter, parallel, double-blind, randomized clinical trial. Patients aged 40 years or older, smokers, or ex-smokers (10 pack-years) with spirometrically confirmed severe COPD (FEV1≤50% predicted and FEV1/FVC ratio<0.7) and diagnosed with an acute exacerbation of chronic bronchitis were enrolled in the study. Patients were randomized to receive prulifloxacin 600mg once a day or levofloxacin 500mg once a day for 7 days. Measurements and main results: The primary outcome measure was clinical assessment at the TOC visit (7-10 days after the end of treatment) of signs and symptoms of exacerbation, namely sputum purulence, sputum volume, dyspnoea, cough and body temperature assessed through semi-quantitative scales. The ITT population included 346 (174 prulifloxacin, 172 levofloxacin) out of 351 treated subjects. A total of 161 patients with prulifloxacin (92.5%) and 166 with levofloxacin (96.5%) were considered cured at TOC (the difference in the percentage of cured patients was -3.98 with 95%CI of -8.76; 0.79). At the 6-month follow-up, the rates of patients with no relapse of AECB were higher than 95% in both the prulifloxacin and levofloxacin groups. Conclusions: Both prulifloxacin and levofloxacin showed efficacy rates higher than 90% in the treatment of severe COPD patients with exacerbations of chronic bronchitis, with no statistically significant differences between the two antibiotics. The long-term follow-up confirmed a very low incidence of relapse, endorsing the appropriateness of this therapeutic approach.EUDRACT no. 2006-004167-56. © 2013 Elsevier Ltd.
Ombrato R.,ACRAF S.p.A. |
Cazzolla N.,ACRAF S.p.A. |
Mancini F.,ACRAF S.p.A. |
Mangano G.,ACRAF S.p.A.
Journal of Chemical Information and Modeling | Year: 2015
An in silico screening procedure was performed to select new inhibitors of glycogen synthase kinase 3β (GSK-3β), a serine/threonine protein kinase that in the last two decades has emerged as a key target in drug discovery, having been implicated in multiple cellular processes and linked with the pathogenesis of several diseases. GSK-3β inhibitors might prove useful as therapeutic compounds in the treatment of conditions associated with elevated levels of enzyme activity, such as type-2 diabetes and neurological disorders, for example, Alzheimers disease, bipolar disorder, neuronal cell death, stroke, and depression. In this work, virtual screening studies were applied to proprietary compound libraries, and the functional activities of selected compounds were assayed on human GSK-3β. The in silico screening procedure enabled the identification of eight hit compounds showing pIC50 values ranging from 4.9 to 5.5. X-ray crystallographic studies resulted in a 2.50 Å three-dimensional structure of GSK-3β complexed with one of the selected compounds, confirming that the inhibitor interacts with the enzyme according to the docking hypothesis. Importantly, molecular docking was able to find a new chemical scaffold for GSK-3β inhibition, providing grounds for rational structure-based design aimed at further optimization of the initial hits. © 2015 American Chemical Society.
Alisi M.A.,A.C.R.A.F. S.p.A |
Brufani M.,University of Rome La Sapienza |
Cazzolla N.,A.C.R.A.F. S.p.A |
Ceccacci F.,University of Rome La Sapienza |
And 11 more authors.
Tetrahedron | Year: 2012
Biochemical studies suggest a direct relationship between the radical scavenging activity of paracetamol (I) and its antipyretic and analgesic action. To evaluate the effect of chemical modifications on the radical scavenging activity of compounds of type I, analogues 1-14 were prepared and submitted to a stable free radical (DPPH; 1,1-diphenyl-2-picryl-hydrazyl) assay. All paracetamol derivatives showed a significant higher efficiency than the parent compound. This study showed that radical scavenging activity can be increased by decreasing the phenolic ortho substituents steric hindrance or by introducing substituents on the acyl moiety like an indazole ring or the ionic N-methyl morpholinium group. A significant activating effect was also observed by replacing the 1,4-acylamidophenol with a 1,4-acylamidonaphthol system. © 2012 Elsevier Ltd. All rights reserved.
Rosignoli M.T.,ACRAF SpA |
Di Loreto G.,ACRAF SpA |
Dionisio P.,ACRAF SpA
Clinical Drug Investigation | Year: 2010
Background and Objective: Prulifloxacin, a broad-spectrum fluoroquinolone, is quantitatively transformed after oral administration into ulifloxacin, the active metabolite. On the basis of preclinical data suggesting that prulifloxacin is not likely to prolong the QT interval, a trial to assess the potential effects of prulifloxacin on QT and corrected QT (QTc) interval in humans was performed. Methods: Fifty-two healthy subjects were randomized into three groups to receive prulifloxacin 600 mg, moxifloxacin 400mg and placebo once daily for 5 days, using a crossover, double-blind versus placebo, moxifloxacin-controlled study. At baseline and days 1 and 5, three 12-lead digital ECGs were recorded before and up to 24 hours after dosing at nine predefined timepoints. Blood samples were also collected at each treatment timepoint. ECG data were analysed in a blinded manner by a centralized laboratory using skilled readers. QT values were corrected for heart rate using an individual correction method (QTcI) as the primary variable, and Fridericias method as reference. Results: In forty-eight subjects who completed the study, compared with placebo, prulifloxacin had no relevant effect on cardiac repolarization, with the largest mean QTcI increase being 3.97 ms (one-sided 95% CI 0.01, 7.93), whereas moxifloxacin demonstrated the expected positive effect (maximum mean QTcI increase of 12.0 ms, one-sided 95% CI 8.66, 15.34), thus demonstrating the good sensitivity of the study. A statistically significant correlation between QTcI changes and plasma concentrations was found for moxifloxacin but not for ulifloxacin. Conclusion: Prulifloxacin at steady state after therapeutic doses has no significant effects on the QTc interval and thus should prove to have no cardiac liability. © 2010 Adis Data Information BV. All rights reserved.
PubMed | ACRAF S.p.A.
Type: Journal Article | Journal: Journal of chemical information and modeling | Year: 2015
An in silico screening procedure was performed to select new inhibitors of glycogen synthase kinase 3 (GSK-3), a serine/threonine protein kinase that in the last two decades has emerged as a key target in drug discovery, having been implicated in multiple cellular processes and linked with the pathogenesis of several diseases. GSK-3 inhibitors might prove useful as therapeutic compounds in the treatment of conditions associated with elevated levels of enzyme activity, such as type-2 diabetes and neurological disorders, for example, Alzheimers disease, bipolar disorder, neuronal cell death, stroke, and depression. In this work, virtual screening studies were applied to proprietary compound libraries, and the functional activities of selected compounds were assayed on human GSK-3. The in silico screening procedure enabled the identification of eight hit compounds showing pIC50 values ranging from 4.9 to 5.5. X-ray crystallographic studies resulted in a 2.50 three-dimensional structure of GSK-3 complexed with one of the selected compounds, confirming that the inhibitor interacts with the enzyme according to the docking hypothesis. Importantly, molecular docking was able to find a new chemical scaffold for GSK-3 inhibition, providing grounds for rational structure-based design aimed at further optimization of the initial hits.
PubMed | ACRAF SpA
Type: Journal Article | Journal: The journal of vascular access | Year: 2013
The persistence of a left superior vena cava is the result of a lack of an embryological involution of the left anterior cardinal vein. This anomaly is very rare: about 0.3% of the general population. Its incidence increases remarkably from 3-10% in those patients affected with congenital heart disease. Described herein is a case of persistent left superior vena cava, discovered by chance, following the placement of a central venous catheter for hemodialysis. A chest X-ray in projection back-forward showed the central venous catheter along the left sternal margin simulating a placement in the aorta artery. This clinical picture, as described in the literature, is often accompanied by other anatomical anomalies, in our case, by the congenital agenesis of a solitary pelvic kidney. In agreement with the literature and in contrast with what has been reported recently, we sustain that a central venous catheter placed, for any reason, in the persistent left superior vena cava must be removed immediately because it can induce hyperkinetic arrhythmia and cardiac arrest as in our case. Our case report should be a warning that lack of awareness of the anomalies of the big central veins can cause a rise in morbidity.