7 research outputs found

    Targeting eosinophils in respiratory diseases: Biological axis, emerging therapeutics and treatment modalities

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    Eosinophils are bi-lobed, multi-functional innate immune cells with diverse cell surface receptors that regulate local immune and inflammatory responses. Several inflammatory and infectious diseases are triggered with their build up in the blood and tissues. The mobilization of eosinophils into the lungs is regulated by a cascade of processes guided by Th2 cytokine generating T-cells. Recruitment of eosinophils essentially leads to a characteristic immune response followed by airway hyperresponsiveness and remodeling, which are hallmarks of chronic respiratory diseases. By analysing the dynamic interactions of eosinophils with their extracellular environment, which also involve signaling molecules and tissues, various therapies have been invented and developed to target respiratory diseases. Having entered clinical testing, several eosinophil targeting therapeutic agents have shown much promise and have further bridged the gap between theory and practice. Moreover, researchers now have a clearer understanding of the roles and mechanisms of eosinophils. These factors have successfully assisted molecular biologists to block specific pathways in the growth, migration and activation of eosinophils. The primary purpose of this review is to provide an overview of the eosinophil biology with a special emphasis on potential pharmacotherapeutic targets. The review also summarizes promising eosinophil-targeting agents, along with their mechanisms and rationale for use, including those in developmental pipeline, in clinical trials, or approved for other respiratory disorders

    Exploiting the natural poly(3-hydroxyalkanoates) production capacity of Antarctic Pseudomonas strains: from unique phenotypes to novel biopolymers

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    Extreme environments are a unique source of microorganisms encoding metabolic capacities that remain largely unexplored. In this work, we isolated two Antarctic bacterial strains able to produce poly(3-hydroxyalkanoates) (PHAs), which were classified after 16S rRNA analysis as Pseudomonas sp. MPC5 and MPC6. The MPC6 strain presented nearly the same specific growth rate whether subjected to a temperature of 4 °C 0.18 (1/h) or 30 °C 0.2 (1/h) on glycerol. Both Pseudomonas strains produced high levels of PHAs and exopolysaccharides from glycerol at 4 °C and 30 °C in batch cultures, an attribute that has not been previously described for bacteria of this genus. The MPC5 strain produced the distinctive medium-chain-length-PHA whereas Pseudomonas sp. MPC6 synthesized a novel polyoxoester composed of poly(3-hydroxybutyrate-co-3-hydroxyhexanoate-co-3-hydroxyoctanoate-co-3-hydroxydecanoate-co-3-hydroxydodecanoate). Batch bioreactor production of PHAs in MPC6 resulted in a titer of 2.6 (g/L) and 1.3 (g/L), accumulating 47.3% and 34.5% of the cell dry mass as PHA, at 30 and 4 °C, respectively. This study paves the way for using Antarctic Pseudomonas strains for biosynthesizing novel PHAs from low-cost substrates such as glycerol and the possibility to carry out the bioconversion process for biopolymer synthesis without the need for temperature control

    Vaccinazione antinfluenzale degli operatori sanitari presso l\u2019IRCCS AOU San Martino-IST di Genova: progetto-pilota di counselling e offerta attiva direttamente presso reparti a elevato rischio

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    Introduzione: La vaccinazione antinfluenzale \ue8 uno strumentofondamentale per la prevenzione dell\u2019influenza in ambito sa-nitario e la sua somministrazione agli Operatori Sanitari (OS)\ue8 raccomandata in oltre 40 Paesi, inclusi gli Stati Uniti d\u2019Ame-rica e molti Paesi dell\u2019Unione Europea. Nonostante questeraccomandazioni, in Italia la compliance degli OS alla vacci-nazione antinfluenzale \ue8 ampiamente inadeguata. Metodi.Apartire dalla stagione 2005/06, \ue8 stato effettuato un progettorivolto all\u2019incremento dei tassi di copertura della vaccinazioneantinfluenzale stagionale tra gli OS che lavorano pressol\u2019IRCCS AOU San Martino-IST di Genova, Italia, ospedale ter-ziario universitario, centro di riferimento regionale per acuticon 1300 posti letto. Risultati.Il tasso medio di copertura vac-cinale registrato nel periodo 2006-2013 \ue8 risultato pari al21,6%, con variazioni comprese tra l\u201911% e il 34%. Durantel\u2019ultima stagione influenzale (2013/14), i tassi di copertura vac-cinale per tipo di occupazione sono risultati pari al 30% tra imedici, 11% tra gli infermieri e 9% nelle restanti categorie diOS. Discussione.Nonostante quasi un decennio di interventi,i tassi di copertura vaccinale registrati nel nostro ospedale ri-mangono costantemente insoddisfacenti e molto distanti dal-l\u2019obiettivo minimo del 75% definito dal Ministero della Salute.Ulteriori interventi sono necessari per prevenire il rischio infettivo legato all\u2019influenza per gli OS e per i pazienti e risultafondamentale identificare e implementare nuove strategievolte all\u2019aumento della compliance degli OS, particolarmentedegli infermieri, alla vaccinazione antinfluenzale.Background.Influenza vaccination is a fundamental tool forthe prevention of influenza in healthcare settings and its ad-ministration to healthcare workers (HCWs) is recommendedin more than 40 countries including United States of Americaand many countries of the European Union. Despite these rec-ommendations, in Italy the compliance of HCWs to influenzavaccination is largely inadequate. Methods.Since the 2005/06season, a comprehensive multifaceted intervention projectaimed at increasing the seasonal influenza vaccination cover-age rates among HCWs was performed at the IRCCS AOU SanMartino IST teaching hospital in Genoa, Italy, the regional ter-tiary adult acute-care reference center with a 1300 bed capac-ity. Results.The average influenza vaccination coverage rateduring the period 2006-2013 was 21,6%, ranging between 11%and 34%. During the last influenza season (2013/14), vaccina-tion coverage rates by occupation type resulted 30% amongphysicians, 11% among nurses and 9% among other clinicalpersonnel. Discussion.Despite almost a decade of efforts, thevaccination coverage rates registered at our hospital steadilyremain unsatisfactory and very distant by the minimum ob-jective of 75% defined by the Italian Ministry of Health. Fur-ther efforts are necessary to prevent the risk of influenzaamong HCWs and patients and novel strategies need to beidentified and implemented in order to increase the compli-ance of HCWs, particularly nurses, with the seasonal influenzavaccinatio

    Safety and tolerability of 13-valent pneumococcal conjugate vaccine in the elderly: An observational study in Liguria Region, Italy

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    Background: In September 2011 the European Medical Agency authorized the use of 13-valent pneumococcal conjugate vaccine (PCV13) in adults aged \ue2\u89\ua550 years. The same occurred in the US in December 2011 when the Food and Drug Administration approved the use of PCV13 in the same target age-group with indication for the prevention of invasive pneumococcal diseases and community acquired pneumonia sustained by the serotypes contained in the vaccine. The Liguria Region, in Italy, implemented in 2013 an active and free of charge immunization strategy with PCV13 among adults affected by specific risk conditions and the elderly aged \ue2\u89\ua570 years. Methods: An observational study was performed in order to assess the safety and tolerability of PCV13 among elderly dwelling in the metropolitan area of Genoa, the capital city of Liguria Region. Eligible subjects, who received PCV13 following the public health immunization campaign at the Local Health Unit 3 of Genoa, provided a written informed consent to take part in the study. Eight-hundred-seventy-one subjects were enrolled between October 2013 and May 2014: all were monitored by qualified healthcare personnel for at least 30 min after vaccination at the outpatient clinics, in order to assess any possible sudden reaction. The occurrence of a series of local and systemic solicited reactions and of any unsolicited Adverse Events (AEs) was monitored using a self-administered clinical diary and by regular phone contacts up to 14 and 21 d following immunization, respectively. Moreover, a 6-months follow-up following vaccination was planned in order to monitor Severe Adverse Events (SAEs). Results: No sudden reaction occurred in vaccinees at the outpatient clinics. Pain (27.4%) was the most frequent reaction reported by subjects at the injection site, while new muscle pain (13.6%), fatigue (10.7%), and headache (9.9%) resulted the most common systemic reactions. Rates of the main reactions reported in this on-field study resulted generally lower than those registered in clinical trials performed in the elderly. The incidence of fever (2.2%) following vaccination was low at values superimposable to that reported in previous studies. Conclusion: This observational study showed a good safety and tolerability of PCV13 among the elderly in routine clinical practice further confirming the evidence coming from clinical trials in the same age-group

    Acceptance and safety of the intradermal influenza vaccine among the elderly in Italy: An on-field national study

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    Introduction: An observational multicenter study was carried out in Italy, to evaluate the acceptability and safety of the new intradermal (ID) influenza vaccine (IntanzaR, Sanofi Pasteur SA, Lyon, France) among subjects aged 65 60 years, compared with that of other intramuscular (IM) influenza vaccines. Compliance with the use of the ID vaccine by healthcare professionals was also assessed. Methods: A previously validated and self-administered questionnaire, Vaccinees' Perception of Injection (VAPI\ua9), consisting of 21 questions, mainly focused on four dimensions (bother, arm movements, sleep, and acceptability), was administered to > 1,600 individuals with spontaneous access to outpatient clinics, located in Northern, Central, and Southern Italy, to evaluate the acceptance of the vaccines. Occurrence of solicited and unsolicited side effects and of serious adverse events was assessed in a subset of subjects (n = 500), using a clinical diary filled in by vaccinees following immunization. Compliance with the new ID vaccine by healthcare professionals was investigated using an ad-hoc questionnaire. Results: A very favorable opinion concerning the acceptability of both the vaccines under survey, with the most positive answers ranging between 75.5% and 94.9%, was registered within the study population. Also the compliance by healthcare professionals (n = 130) with the novel ID vaccine was favorable. No serious adverse event occurred during the 6-month follow-up period. The frequency of solicited systemic reactions was comparable between the two study groups, while solicited local reactions were significantly higher in the ID-vaccine group than in the IM-vaccine group, even if at values lower than those reported in phase 3 clinical trials (ranges = 18.5-32.6% vs. 29.5-70.9%). These local events were mild and transient, thus without any clinical relevance. Conclusion: The novel ID influenza vaccine can be widely recommended in clinical practice, representing a useful tool to improve immunization coverage rates, and thus the control of influenza. \ua9 Springer Healthcare 2012
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