Imaging con biofluorescenza nelle ulcere cutanee croniche.

L'infezione è uno dei fattori coinvolti nell'infiammazione delle ferite croniche, e dipende dalla difesa dell'ospite e dalla virulenza dei batteri. La detenzione con prodotti antisettici, lo sbrigliamento e l'utilizzo di vari tipi di medicazioni come all'argento, medicazioni a captazione batterica, medicazioni allo iodio, al miele, olio iperossidato e medicazioni al poliesametilene biguanide sono stati usati localmente per ridurre la carica batterica. Un altro approccio funzionale per combattere l'infezione delle ferite è il bendaggio all'ossido di zinco (Unna Boot)che ha mostrato un effetto importante per l'autodebridemen, per la formazione di collagene e per l'azione antibatterica. Lo zinco è più efficace contro i batteri Gram positivi ma inibisce anche i batteri negativi e vari batteri aerobi e anaerobi. Il tampone e la biopsia microbiologica sono utilizzati come gold standard per la valutazione qualitativa e quantitativa dei batteri. MolecuLight i:X è un dispositivo portatile che permette una valutazione dell'area della ferita e dei batteri della superficie della ferita (>104 CFU/g) in modo non invasivo e in tempo reale. MolecuLight i:X valuta la fluorescenza emessa dai batteri e da diversi tipi di tessuto. Lo Pseudomonas e altri gram negativi emettono una fluorescenza ciano e lo Staphylococcus aureus e i batteri gram positivi emettono una fluorescenza rossa. Lo scopo del nostro studio era di valutare con MolecuLight i:X la riduzione della carica batterica in 3 diversi gruppi di trattamento locale differente composti ciascuno da 10 pazienti

TEST DELLE ENDOTOSSINE BATTERICHE: Studio degli aspetti critici e utilizzo su matrici iniettabili

Le endotossine presenti nella membrana esterna dei batteri Gram negativi, possono avere un effetto pirogeno. Perciò le farmacopee stabiliscono che per i prodotti farmaceutici iniettabili si debba garantire un contenuto endotossinico tale da non determinare reazioni febbrili (E.P 5.1.10) e stabiliscono i metodi per la loro determinazione (E.P 2.6.14). Il test delle Endotossine Batteriche (BET), comunemente conosciuto con il nome di LAL Test (Limulus Amebocyte Lysate Test), si basa sull’utilizzo di un lisato di amebociti derivante dall’emolinfa di Limulus polyphemus, il quale contiene enzimi che, in presenza di endotossina, si attivano a cascata dando luogo alla formazione di un coagulo. I metodi di farmacopea possono essere qualitativi o quantitativi e quest’ultimi possono essere turbidimetrici o cromogenici. Lo scopo della tesi è stato quello di implementare una nuova piattaforma che consente la quantificazione delle endotossine batteriche con il metodo cinetico-cromogenico. La suddetta piattaforma, che usa cartucce precalibrate, è stata introdotta a fianco di una che si basa sul metodo cinetico turbidimetrico, e che è in uso dal 1995 e perciò risulta superata. Dal momento che i recenti orientamenti della Comunità Europea in merito alle norme di buona fabbricazione suggeriscono l’introduzione dell’analisi del rischio a fianco delle GMP (ICH Q9, EU GMP), abbiamo deciso, ai fini di quanto precedentemente detto, di applicare l’analisi del rischio al processo di analisi a partire dal processing fino alla valutazione dei risultati e includendo la gestione dei reagenti. Per l’analisi del rischio è stata applicata la metodologia HACCP (Hazard Analysis and Critical Control Point) seguendo i suoi principi fondamentali e precedendola con una fase preliminare di studio del processo, come suggerito dal documento del WHO. Per i seguenti Punti Critici di Controllo (CCP), che sono gestiti in maniera eccessivamente prudente a causa della mancanza di dati sperimentali e/o bibliografici, è stato deciso di eseguire delle prove sperimentali per verificare la possibilità di una gestione meno stringente, se possibile, e per stabilire i limiti e le modalità di monitoraggio: - La conservazione dei diluenti, utilizzati per il BET, dopo l’apertura, - L’utilizzo di materiali in plastica in aggiunta a quelli in vetro borosilicato - La precisione di strumenti non certificati dal produttore, in particolare per la vetreria graduata - Il tempo di conservazione di soluzioni campione e standard, una volta preparate Inoltre l’impiego della nuova piattaforma per il BET, inizialmente utilizzata per la ricerca di endotossine nell’acqua distillata (WFI), ha portato alla necessità di verificare se fosse possibile utilizzarla anche per l’analisi su: - Prodotti finiti (fiale con matrici iniettabili) - Materie prime - Superfici di lavoro Come premesso, le prove, ad eccezione della vetreria graduata, sono state eseguite mediante test biologici, in cui sono stati analizzati campioni contaminati con endotossina standard e non, valutandone il recupero endotossinico e confrontando i valori di endotossina al tempo zero e al termine del periodo di conservazione. I risultati sono i seguenti: - Per i diluenti si è stabilito: il limite endotossinico (<0,005 UI/ml), il metodo per il controllo di qualità e le condizioni di conservazione (2÷8 °C, per 14 o 30 giorni a seconda del tipo di diluente). - Per i materiali in plastica si è stabilito: il limite endotossinico (<0,005 UI/ml) e si è definito il metodo per il controllo di qualità. - Per la vetreria graduata si è stabilito: la precisione accettabile ed il metodo per il controllo di qualità. - Per i campioni è stato stabilito il metodo di analisi e il tempo di conservazione (≤ 3 ore) per il procedimento di analisi - Per le superfici di lavoro si è stabilito il metodo di analisi. In conclusione l’utilizzo dell’HACCP ha permesso di affrontare lo studio del processo di analisi finalizzato alla determinazione delle endotossine batteriche in maniera meno soggettiva e più mirata; consentendo di rilevare i punti critici, di mettere questi ultimi sotto controllo in maniera meno rigida, quando possibile e di determinarne le condizioni per il loro futuro monitoraggio (metodi, limiti e frequenza)

Blue light emission in the management of hard to heal wounds: a case series

Backgroun: Blue light (400 and 450 nm) contributes to bringing the inflammatory phase under control, increases angiogenesis, stimulates the metabolism of all cellular processes, reduces scar formation, increases collagen production, and decreases the bacterial burden. Methods: The aim of this study was to promote the healing process in 20 hard-to-heal wounds using a portable light-emitting diodes device that emits blue light (Emoled™). The primary endpoint of the study was to calculate in the three etiologic groups the reduction in wound size by the average delta area in square centimeters and as a percentage, and by the average healing rate (mm/Days). The secondary endpoint was to assess the wound bed score and to assess patients' pain (numerical rating scale). Results: At week 4 the average healing rate was 0.098 mm/days for venous leg ulcers, 0.353 mm/days for traumatic ulcers, and 0.09 mm/days for vasculitis. Overall 16 patients had a reduction in wound size, two patients were completely healed, and there was no improvement in two patients. At week 4, the average wound bed score had increased to 12.8 and average pain had decreased to 2.35. Almost all patients (n=19) showed pain reduction, and all the patients increased wound bed score. Conclusions: The blue LED device is promising in terms of promoting wound healing, improving WBS and reducing pain in patients affected by long-term wounds that do not respond to standard treatment

Development of Methods for Recovering Endotoxins from Surfaces and from Air in Production Environment of Injectable Drugs

The aim of this work is to develop and validate methods for quantifying endotoxins on surfaces and in the air of the manufacturing environment of injectable drugs, in order to use them to evaluate the quality of the process and the risk for the products processed therein. The method for recovering endotoxins from surfaces is a direct method that provides sampling surfaces by swabbing and extraction of endotoxins from the swabs with an appropriate diluent, while the method for airborne endotoxins provides an air-active sampling on a glass fiber filter and endotoxins extraction with an appropriate diluent.LAY ABSTRACT: Bacterial endotoxins are present in the environments devoted to the manufacturing of injectable drugs and could be a real risk for the quality and the safety of such drugs. So the quality control laboratories should have analytical methods to recover bacterial endotoxins from environmental samples. The aim of this publication is to show how we succeeded in developing and validating methods to quantify bacterial endotoxins on surfaces and in the air

5% Lidocaine Hydrochloride Cream for Wound Pain Relief: A Multicentre Observational Study

Background: Lidocaine hydrochloride is frequently used for management of painful wounds. This prospective, multicentre study examined the effects of 5% lidocaine cream on wound pain relief. Material and methods: The study included 78 patients with painful wounds treated with 5% Lidocaine cream for two weeks in two Italian Hospitals. Patients' perception of pain was recorded by, using the 5-point Visual Rate Scale and the 11-point Numerical Pain Rating Scale. All medications and adverse events were evaluated in a daily diary. The primary outcome of the study was establishing the wound pain relief based on the results of 5-VRS and pain intensity based on the 11-NPRS testing from baseline to the end of treatment. Clinical aspects and adverse events were also collected. Results: Seventy-eight patients had a median age of 67.5 years (range 18-96 years). 62.8% were women. The wounds included traumatic wounds (n = 39), venous ulcers (n = 25), post-surgical wounds (n = 6) pyoderma gangrenosum (n = 6), vasculitis (n = 1) and pressure ulcer (n = 1). The intensity of pain significantly decreased from the baseline level established at the beginning of treatment (mean score 6.7 - 1.90) - to the level at end of treatment (3.0 - 2.23-; p &lt; 0.0001). 9 patients prematurely stopped the treatment for healing (n = 4), wound improvement (n = 2) and adverse events related to the treatment. (n = 3). 13 patients presented a total of 25 adverse events, 4 of them were related to the treatment. Conclusion: The treatment of painful wounds with 5% Lidocaine Cream for 14 days resulted in reduced pain intensity, and showed high safety and tolerability

5% Lidocaine Hydrochloride Cream for Wound Pain Relief: A Multicentre Observational Study

Background Lidocaine hydrochloride is frequently used for management of painful wounds. This prospective, multicentre study examined the effects of 5% lidocaine cream on wound pain relief. Material and methods The study included 78 patients with painful wounds treated with 5% Lidocaine cream for two weeks in two Italian Hospitals. Patients’ perception of pain was recorded by, using the 5-point Visual Rate Scale and the 11-point Numerical Pain Rating Scale. All medications and adverse events were evaluated in a daily diary. The primary outcome of the study was establishing the wound pain relief based on the results of 5-VRS and pain intensity based on the 11-NPRS testing from baseline to the end of treatment. Clinical aspects and adverse events were also collected. Results Seventy-eight patients had a median age of 67.5 years (range 18-96 years). 62.8% were women. The wounds included traumatic wounds (n = 39), venous ulcers (n = 25), post-surgical wounds (n = 6) pyoderma gangrenosum (n = 6), vasculitis (n = 1) and pressure ulcer (n = 1). The intensity of pain significantly decreased from the baseline level established at the beginning of treatment (mean score 6.7 − 1.90) - to the level at end of treatment (3.0 − 2.23-; p < 0.0001). 9 patients prematurely stopped the treatment for healing (n = 4), wound improvement (n = 2) and adverse events related to the treatment. (n = 3). 13 patients presented a total of 25 adverse events, 4 of them were related to the treatment. Conclusion The treatment of painful wounds with 5% Lidocaine Cream for 14 days resulted in reduced pain intensity, and showed high safety and tolerability

MEDICAL SCIENCE. GISSI-2: A factorial randomised trial of alteplase versus streptokinase and heparin versus no heparin among 12 490 patients with acute myocardial infarction

A multicentre, randomised, open trial with a 2 x 2 factorial design was conducted to compare the benefits and risks of two thrombolytic agents, streptokinase (SK, 1\ub75 MU infused intravenously over 30-60 min) and alteplase (tPA, 100 mg infused intravenously over 3 h) in patients with acute myocardial infarction admitted to coronary care units within 6 h from onset of symptoms. The patients were also randomised to receive heparin (12 500 U subcutaneously twice daily until discharge from hospital, starting 12 h after beginning the tPA or SK infusion) or usual therapy. All patients without specific contraindications were given atenolol (5-10 mg iv) and aspirin (300-325 mg a day). The end-point of the study was the combined estimate of death plus severe left ventricular damage. 12 490 patients were randomised to four treatment groups (SK alone, SK plus heparin, tPA alone, tPA plus heparin). No specific differences between the two thrombolytic agents were detected as regards the combined end-point (tPA 23\ub71%; SK 22\ub75%; relative risk 1\ub704, 95% Cl 0\ub795-1\ub713), nor after the addition of heparin to the aspirin treatment (hep 22\ub77%, no hep 22\ub79%; RR 0\ub799, 95% Cl 0\ub791-1\ub708). The outcome of patients allocated to the four treatment groups was similar with respect to baseline risk factors such as age, Killip class, hours from onset of symptoms, and site and type of infarct. The rates of major in-hospital cardiac complications (reinfarction, post-infarction angina) were also similar. The incidence of major bleeds was significantly higher in SK and heparin treated patients (respectively, tPA 0\ub75%, SK 1\ub70%, RR 0\ub757, 95% Cl 0\ub738-0\ub785; hep 1\ub70%, no hep 0\ub76%, RR 1\ub764, 95% Cl 1\ub709-2\ub745), whereas the overall incidence of stroke was similar in all groups. SK and tPA appear equally effective and safe for use in routine conditions of care, in all infarct patients who have no contraindications, with or without post-thrombolytic heparin treatment. The 8\ub78% hospital mortality of the study population (compared with approximately 13% in the control cohort of the GISSI-1 trial) indicates the beneficial impact of the proven acute treatments for AMI. \ua9 1990

Deep Underground Neutrino Experiment (DUNE), Far Detector Technical Design Report, Volume I Introduction to DUNE

International audienceThe preponderance of matter over antimatter in the early universe, the dynamics of the supernovae that produced the heavy elements necessary for life, and whether protons eventually decay—these mysteries at the forefront of particle physics and astrophysics are key to understanding the early evolution of our universe, its current state, and its eventual fate. The Deep Underground Neutrino Experiment (DUNE) is an international world-class experiment dedicated to addressing these questions as it searches for leptonic charge-parity symmetry violation, stands ready to capture supernova neutrino bursts, and seeks to observe nucleon decay as a signature of a grand unified theory underlying the standard model. The DUNE far detector technical design report (TDR) describes the DUNE physics program and the technical designs of the single- and dual-phase DUNE liquid argon TPC far detector modules. This TDR is intended to justify the technical choices for the far detector that flow down from the high-level physics goals through requirements at all levels of the Project. Volume I contains an executive summary that introduces the DUNE science program, the far detector and the strategy for its modular designs, and the organization and management of the Project. The remainder of Volume I provides more detail on the science program that drives the choice of detector technologies and on the technologies themselves. It also introduces the designs for the DUNE near detector and the DUNE computing model, for which DUNE is planning design reports. Volume II of this TDR describes DUNE's physics program in detail. Volume III describes the technical coordination required for the far detector design, construction, installation, and integration, and its organizational structure. Volume IV describes the single-phase far detector technology. A planned Volume V will describe the dual-phase technology

Deep Underground Neutrino Experiment (DUNE), Far Detector Technical Design Report, Volume II: DUNE Physics

The preponderance of matter over antimatter in the early universe, the dynamics of the supernovae that produced the heavy elements necessary for life, and whether protons eventually decay -- these mysteries at the forefront of particle physics and astrophysics are key to understanding the early evolution of our universe, its current state, and its eventual fate. DUNE is an international world-class experiment dedicated to addressing these questions as it searches for leptonic charge-parity symmetry violation, stands ready to capture supernova neutrino bursts, and seeks to observe nucleon decay as a signature of a grand unified theory underlying the standard model. The DUNE far detector technical design report (TDR) describes the DUNE physics program and the technical designs of the single- and dual-phase DUNE liquid argon TPC far detector modules. Volume II of this TDR, DUNE Physics, describes the array of identified scientific opportunities and key goals. Crucially, we also report our best current understanding of the capability of DUNE to realize these goals, along with the detailed arguments and investigations on which this understanding is based. This TDR volume documents the scientific basis underlying the conception and design of the LBNF/DUNE experimental configurations. As a result, the description of DUNE's experimental capabilities constitutes the bulk of the document. Key linkages between requirements for successful execution of the physics program and primary specifications of the experimental configurations are drawn and summarized. This document also serves a wider purpose as a statement on the scientific potential of DUNE as a central component within a global program of frontier theoretical and experimental particle physics research. Thus, the presentation also aims to serve as a resource for the particle physics community at large

Deep Underground Neutrino Experiment (DUNE) Near Detector Conceptual Design Report

International audienceThe Deep Underground Neutrino Experiment (DUNE) is an international, world-class experiment aimed at exploring fundamental questions about the universe that are at the forefront of astrophysics and particle physics research. DUNE will study questions pertaining to the preponderance of matter over antimatter in the early universe, the dynamics of supernovae, the subtleties of neutrino interaction physics, and a number of beyond the Standard Model topics accessible in a powerful neutrino beam. A critical component of the DUNE physics program involves the study of changes in a powerful beam of neutrinos, i.e., neutrino oscillations, as the neutrinos propagate a long distance. The experiment consists of a near detector, sited close to the source of the beam, and a far detector, sited along the beam at a large distance. This document, the DUNE Near Detector Conceptual Design Report (CDR), describes the design of the DUNE near detector and the science program that drives the design and technology choices. The goals and requirements underlying the design, along with projected performance are given. It serves as a starting point for a more detailed design that will be described in future documents