Anti-Inflammatory Effect of the Natural H2S-Donor Erucin in Vascular Endothelium

Vascular inflammation (VI) represents a pathological condition that progressively affects the integrity and functionality of the vascular wall, thus leading to endothelial dysfunction and the onset of several cardiovascular diseases. Therefore, the research of novel compounds able to prevent VI represents a compelling need. In this study, we tested erucin, the natural isothiocyanate H2S-donor derived from Eruca sativa Mill. (Brassicaceae), in an in vivo mouse model of lipopolysaccharide (LPS)-induced peritonitis, where it significantly reduced the amount of emigrated CD11b positive neutrophils. We then evaluated the anti-inflammatory effects of erucin in LPS-challenged human umbilical vein endothelial cells (HUVECs). The pre-incubation of erucin, before LPS treatment (1, 6, 24 h), significantly preserved cell viability and prevented the increase of reactive oxygen species (ROS) and tumor necrosis factor alpha (TNF-alpha) levels. Moreover, erucin downregulated endothelial hyperpermeability and reduced the loss of vascular endothelial (VE)-Cadherin levels. In addition, erucin decreased vascular cell adhesion molecule 1 (VCAM-1), cyclooxygenase-2 (COX-2) and microsomal prostaglandin E-synthase 1 (mPGES-1) expression. Of note, erucin induced eNOS phosphorylation and counteracted LPS-mediated NF-kappa B nuclear translocation, an effect that was partially abolished in the presence of the eNOS inhibitor L-NAME. Therefore, erucin can control endothelial function through biochemical and genomic positive effects against VI

Characterization of Carbonic Anhydrase IX Interactome Reveals Proteins Assisting Its Nuclear Localization in Hypoxic Cells

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The rapid spread of SARS-COV-2 Omicron variant in Italy reflected early through wastewater surveillance

The SARS-CoV-2 Omicron variant emerged in South Africa in November 2021, and has later been identified worldwide, raising serious concerns. A real-time RT-PCR assay was designed for the rapid screening of the Omicron variant, targeting characteristic mutations of the spike gene. The assay was used to test 737 sewage samples collected throughout Italy (19/21 Regions) between 11 November and 25 December 2021, with the aim of assessing the spread of the Omicron variant in the country. Positive samples were also tested with a real-time RT-PCR developed by the European Commission, Joint Research Centre (JRC), and through nested RT-PCR followed by Sanger sequencing. Overall, 115 samples tested positive for Omicron SARS-CoV-2 variant. The first occurrence was detected on 7 December, in Veneto, North Italy. Later on, the variant spread extremely fast in three weeks, with prevalence of positive wastewater samples rising from 1.0% (1/104 samples) in the week 5-11 December, to 17.5% (25/143 samples) in the week 12-18, to 65.9% (89/135 samples) in the week 19-25, in line with the increase in cases of infection with the Omicron variant observed during December in Italy. Similarly, the number of Regions/Autonomous Provinces in which the variant was detected increased from one in the first week, to 11 in the second, and to 17 in the last one. The presence of the Omicron variant was confirmed by the JRC real-time RT-PCR in 79.1% (91/115) of the positive samples, and by Sanger sequencing in 66% (64/97) of PCR amplicons. In conclusion, we designed an RT-qPCR assay capable to detect the Omicron variant, which can be successfully used for the purpose of wastewater-based epidemiology. We also described the history of the introduction and diffusion of the Omicron variant in the Italian population and territory, confirming the effectiveness of sewage monitoring as a powerful surveillance tool

Farmaci EMEA ed innovazione terapeutica

L’innovazione in farmacoterapia è tema molto attuale e fonte di numerosi dibattiti per quanti, a vario titolo, s’interessano di farmaci: agenzie regolatorie, aziende produttrici, operatori sanitari, ricercatori, pazienti e cittadini. In particolare, le agenzie regolatorie e i “policy-makers”, essendo chiamati a decidere come meglio allocare le risorse economiche disponibili, sono tra i soggetti maggiormente interessati

Six-year activity on approval of compassionate use of medicines by the Ethics Committee of the University Hospital of Bologna (Italy): time to update rules and recommendations

Purpose: Compassionate use of forthcoming drugs has become an increasing pathway through which patients can take advantage of promising medicines. We aimed to analyse the main features of the requests of compassionate use submitted to the Independent Ethics Committee (IEC) of the University Hospital of Bologna in the period 2010\ue2\u80\u932015. Methods: The present analysis concerns the requests of compassionate use received by the IEC in the period 2010\ue2\u80\u932015. For each requested drug, we paired the date of the first request to our IEC with the date(s) of (a) submission to EMA, (b) CHMP positive opinion, and (c) European marketing authorization (if issued). Results: In the period 2010\ue2\u80\u932015, our IEC received compassionate use requests for 610 patients. Most of the requests concerned patients suffering from solid or haematological cancers not responsive to first or second line of treatment. Sixty-five couples of medicine/clinical condition (corresponding to 56 individual medicines) were submitted to our IEC, and 62 of them regarded products following the centralised procedure at the EMA. Twenty-one out of the latter (34%) had already obtained CHMP positive opinion. Conclusions: Our results indicate that compassionate use of forthcoming medicines represents a not negligible portion of the therapies utilized in hospital care. The observed large resort to medicines still on trial may suggest that doctors are more aware with the potential benefits of the new drugs. However, this trend may also indicate an increasing marketing activity of the pharmaceutical industry, addressing to get the clinicians used to the upcoming medicines

Therapeutic innovation in the European Union: analysis of the drugs approved by the EMEA between 1995 and 2003

Since January 1995, all European Union applications for marketing approval for medicinal products derived from biotechnology and other drugs considered potentially innovative follow the EMEA centralized procedure. In order to assess the overall degree of therapeutic innovation of these drugs, we considered, for each approved agent, its target, the availability of previous treatments and the extent of its therapeutic effect. The following scores for therapeutic innovation were assigned through a consensus process: ‘A’ (important), ‘B’ (moderate) and ‘C’ (modest). The overall degree of important/moderate therapeutic innovation was 47% of all therapeutic agents (32% important; 15% moderate). Most (80%) of the EMEA-approved therapeutic agents were for serious diseases. The remaining ones were for risk factors (7%) or nonserious diseases (13%)

Dronedarone-associated acute renal failure: evidence coming from the Italian spontaneous ADR reporting database

AIM To describe cases of acute renal failure (ARF) and of renal failure (RF) from dronedarone retrieved in the general population during post-marketing surveillance through the Italian spontaneous ADR reporting database. METHODS A case by case analysis was performed. Reports codified with the System Organ Class (SOC) term \u2018urinary system disorders\u2019 of the ADR terminology of the World Health Organization associated with dronedarone treatment were selected. RESULTS Out of 124 069 ADR reports, in 55 of them dronedarone was listed as the suspected drug. Among these reports, we identified four cases of ARF, two of RF and three cases of increase of blood creatinine submitted by physicians between October 2010 and December 2011. The patient age was from 61 to 84 years and most cases occurred within the first 13 days of initiation of dronedarone therapy (range 6 days \u2013 2 months). Only one patient received a co-suspected drug labelled for causing ARF. In all reports but one, positive dechallenge was reported. CONCLUSIONS Clinicians should be made aware of the risk of ARF/RF associated with dronedarone and of the need to screen patients appropriately for ARF/RF risk factors before starting dronedarone therapy