The use of Mitomycin-C to reduce synechia in middle meatus in sinus surgery: preliminary results

Synechia is the most frequent complication after sinus surgery and has been reported in up to 36% of cases. Several types of materials have been used to reduce the incidence of synechia, including Mitomycin C (MMC). Objective: This prospective study aimed to assess the effectiveness of topical MMC in the prevention of synechia after sinus surgery in humans. Methods: At the end of surgery, MMC solution (1.0 mg/ml) was topically applied randomly to one of the middle meatuses (MMC group) of 14 patients while saline solution was applied to the contralateral meatus (control group). The author remained blind to the medicated side. Synechiae were classified as partial or total. Results: Three patients had middle meatus synechia in the MMC group (21.43%) versus nine (64.29%) in the control group (p = 0.054). In the MMC group, all three middle meatus synechia were partial, while in the control group there were four partial (28.57%) and five total (35.71%) cases of synechia (p = 0.025). Conclusions: Mitomycin C was not effective in preventing middle meatus synechia, but reduced the probability of total synechia formation.

Re-treatment of previous non-responders and relapsers to interferon plus ribavirin with peginterferon alfa-2a (40KD), ribavirin +/- amantadine in patients with chronic hepatitis C: randomized multicentre clinical trial

Introduction. A large number of patients with chronic hepatitis C have not been cured with interferon-based therapy. Therefore, we evaluated the efficacy of amantadine combined with the standard of care (pegylated interferon plus ribavirin) in patients who had not responded to or had relapsed after 24 weeks of treatment with conventional interferon plus ribavirin. Material and methods. Patients stratified by previous response (i.e., non-response or relapse) were randomized to 48 weeks of open-label treatment with peginterferon alfa-2a (401(D) 180 pg/week plus ribavirin 1,000/1,200 mg/day plus amantadine 200 mg/day (triple therapy), or the standard of care (peginterferon alfa-2a [40KD] plus ribavirin). Results. The primary outcome was sustained virological response (SVR), defined as undetectable hepatitis C virus RNA in serum (< 50 IU/mL) at end of follow-up (week 72). Among patients with a previous non-response, 12/53 (22.6%; 95% confidence interval [CI] 12.3-36.2%) randomized to triple therapy achieved an SVR compared with 16/52 (30.8%; 95% CI 18.7-45.1%) randomized to the standard of care. Among patients with a previous relapse 22/39 (56.4%; 95% CI 39.6-72.2%) randomized to triple therapy achieved an SVR compared with 23/38 (60.5%; 95% CI 43.4-76.0%) randomized to the standard of care. Undetectable HCV RNA (< 50 IU/mL) at week 12 had a high positive predictive value for SVR. A substantial proportion of non-responders and relapsers to conventional interferon plus ribavirin achieve an SVR when re-treated with peginterferon alfa-2a (40KD) plus ribavirin. Conclusion. Amantadine does not enhance SVR rates in previously treated patients with chronic hepatitis C and cannot be recommended in this setting.

Immunogenicity of a meningococcal serogroup C conjugate vaccine in HIV-infected children, adolescents, and young adults

Children and adolescents infected with HIV typically have a lower response to immunization than do those in the general population. In most developed countries, meningococcal serogroup C conjugate vaccine is one of the recommended vaccines for such individuals. However, there have been no studies evaluating the antibody response to this vaccine in HIV-infected children, adolescents or young adults. In this study, we evaluated that response using serum bactericidal antibody (SBA) and enzyme-linked immunosorbent assay, comparing HIV-infected with non-HIV-infected patients, as well as analysing the occurrence of side effects. In non-responders, we assessed the antibody response to revaccination. This clinical trial involved 92 patients between 10 and 20 years of age: 43 HIV-infected patients (HIV+ group) and 49 non-HIV-infected patients (HIV- group). After one dose of the vaccine, 72.1% of the HIV+ group patients and 100% of the HIV- group patients were considered protected. Of the HIV+ group patients who received a second dose of the vaccine, only 40% acquired protection. Overall, 81.4% of the HIV+ group patients acquired protection (after one or two doses of the vaccine). Side effects occurred in 16.3% and 44% of the HIV+ group and HIV- group patients, respectively. Therefore, the meningococcal serogroup C conjugate vaccine proved to be safe and effective for use in HIV-infected children, adolescents, and young adults, although their antibody response was weaker than that shown by non-HIV-infected patients. This indicates the need to discuss changes to the immunization schedule for children, adolescents, and young adults infected with HIV, in order to ensure more effective protection against meningococcal disease. (c) 2012 Elsevier Ltd. All rights reserved.

Prophylactic and Therapeutic Vaccination Using Dendritic Cells Primed with Peptide 10 Derived from the 43-Kilodalton Glycoprotein of Paracoccidioides brasiliensis

Vaccination with peptide 10 (P10), derived from the Paracoccidioides brasiliensis glycoprotein 43 (gp43), induces a Th1 response that protects mice in an intratracheal P. brasiliensis infection model. Combining P10 with complete Freund's adjuvant (CFA) or other adjuvants further increases the peptide's antifungal effect. Since dendritic cells (DCs) are up to 1,000-fold more efficient at activating T cells than CFA, we examined the impact of P10-primed bone-marrow-derived DC vaccination in mice. Splenocytes from mice immunized with P10 were stimulated in vitro with P10 or P10-primed DCs. T cell proliferation was significantly increased in the presence of P10-primed DCs compared to the peptide. The protective efficacy of P10-primed DCs was studied in an intratracheal P. brasiliensis model in BALB/c mice. Administration of P10-primed DCs prior to (via subcutaneous vaccination) or weeks after (via either subcutaneous or intravenous injection) P. brasiliensis infection decreased pulmonary damage and significantly reduced fungal burdens. The protective response mediated by the injection of primed DCs was characterized mainly by an increased production of gamma interferon (IFN-gamma) and interleukin 12 (IL-12) and a reduction in IL-10 and IL-4 compared to those of infected mice that received saline or unprimed DCs. Hence, our data demonstrate the potential of P10-primed DCs as a vaccine capable of both the rapid protection against the development of serious paracoccidioidomycosis or the treatment of established P. brasiliensis disease.

Failure to reduce C-reactive protein levels more than 25% in the last 24 hours before intensive care unit discharge predicts higher in-hospital mortality: A cohort study

Purpose: To discharge a patient from the intensive care unit (ICU) is a complex decision-making process because in-hospital mortality after critical illness may be as high as up to 27%. Static C-reactive protein (CRP) values have been previously evaluated as a predictor of post-ICU mortality with conflicting results. Therefore, we evaluated the CRP ratio in the last 24 hours before ICU discharge as a predictor of in-hospital outcomes. Methods: A retrospective cohort study was performed in 409 patients from a 6-bed ICU of a university hospital. Data were prospectively collected during a 4-year period. Only patients discharged alive from the ICU with at least 72 hours of ICU length of stay were evaluated. Results: In-hospital mortality was 18.3% (75/409). Patients with reduction less than 25% in CRP concentrations at 24 hours as compared with 48 hours before ICU discharge had a worse prognosis, with increased mortality (23% vs 11%, P = .002) and post-ICU length of stay (26 [7-43] vs 11 [5-27] days, P = .036). Moreover, among hospital survivors (n = 334), patients with CRP reduction less than 25% were discharged later (hazard ratio, 0.750; 95% confidence interval, 0.602-0.935; P = .011). Conclusions: In this large cohort of critically ill patients, failure to reduce CRP values more than 25% in the last 24 hours of ICU stay is a strong predictor of worse in-hospital outcomes. (C) 2012 Elsevier Inc. All rights reserved.

Dual effect of Lutzomyia longipalpis saliva on Leishmania braziliensis infection is mediated by distinct saliva-induced cellular recruitment into BALB/c mice ear

Abstract Background Leishmania parasites are transmitted to their vertebrate hosts by infected Phlebotomine sand flies during the blood meal of the flies. Sand fly saliva is known to enhance Leishmania spp. infection, while pre-exposure to saliva protects mice against parasitic infections. In this study, we investigated the initial inflammatory leucocyte composition induced by one or three inocula of salivary gland extract (SGE) from Lutzomyia longipalpis in the presence or absence of Leishmania braziliensis. Results We demonstrated that inoculating SGE once (SGE-1X) or three times (SGE-3X), which represented a co-inoculation or a pre-exposure to saliva, respectively, resulted in different cellular infiltrate profiles. Whereas SGE-1X led to the recruitment of all leucocytes subtypes including CD4+ T cells, CD4+CD25+ T cells, dendritic cells, macrophages and neutrophils, the immune cell profile in the SGE-3X group differed dramatically, as CD4+ T cells, CD4+CD25+ T cells, dendritic cells, macrophages and neutrophils were decreased and CD8+ T cells were increased. The SGE-1X group did not show differences in the ear lesion size; however, the SGE-1X group harbored a higher number of parasites. On the other hand, the SGE-3X group demonstrated a protective effect against parasitic disease, as the parasite burden was lower even in the earlier stages of the infection, a period in which the SGE-1X group presented with larger and more severe lesions. These effects were also reflected in the cytokine profiles of both groups. Whereas the SGE-1X group presented with a substantial increase in IL-10 production, the SGE-3X group showed an increase in IFN-γ production in the draining lymph nodes. Analysis of the inflammatory cell populations present within the ear lesions, the SGE-1X group showed an increase in CD4+FOXP3+ cells, whereas the CD4+FOXP3+ population was reduced in the SGE-3X group. Moreover, CD4+ T cells and CD8+ T cells producing IFN-γ were highly detected in the ears of the SGE-3X mice prior to infection. In addition, upon treatment of SGE-3X mice with anti-IFN-γ monoclonal antibody, we observed a decrease in the protective effect of SGE-3X against L. braziliensis infection. Conclusions These results indicate that different inocula of Lutzomyia longipalpis salivary gland extract can markedly modify the cellular immune response, which is reflected in the pattern of susceptibility or resistance to Leishmania braziliensis infection.

Metabolism of plasma cholesterol and lipoprotein parameters are related to a higher degree of insulin sensitivity in high HDL-C healthy normal weight subjects

Abstract Background We have searched if plasma high density lipoprotein-cholesterol (HDL-C) concentration interferes simultaneously with whole-body cholesterol metabolism and insulin sensitivity in normal weight healthy adult subjects. Methods We have measured the activities of several plasma components that are critically influenced by insulin and that control lipoprotein metabolism in subjects with low and high HDL-C concentrations. These parameters included cholesteryl ester transfer protein (CETP), phospholipid transfer protein (PLTP), lecithin cholesterol acyl transferase (LCAT), post-heparin lipoprotein lipase (LPL), hepatic lipase (HL), pre-beta-1HDL, and plasma sterol markers of cholesterol synthesis and intestinal absorption. Results In the high-HDL-C group, we found lower plasma concentrations of triglycerides, alanine aminotransferase, insulin, HOMA-IR index, activities of LCAT and HL compared with the low HDL-C group; additionally, we found higher activity of LPL and pre-beta-1HDL concentration in the high-HDL-C group. There were no differences in the plasma CETP and PLTP activities. Conclusions These findings indicate that in healthy hyperalphalipoproteinemia subjects, several parameters that control the metabolism of plasma cholesterol and lipoproteins are related to a higher degree of insulin sensitivity.

Modellazione bidimensionale della propagazione nell'entroterra della inondazione da mare negli scenari dei previsti cambiamenti climatici

Le ricerche di carattere eustatico, mareografico, climatico, archeologico e geocronologico, sviluppatesi soprattutto nell’ultimo ventennio, hanno messo in evidenza che gran parte delle piane costiere italiane risulta soggetta al rischio di allagamento per ingressione marina dovuta alla risalita relativa del livello medio del mare. Tale rischio è la conseguenza dell’interazione tra la presenza di elementi antropici e fenomeni di diversa natura, spesso difficilmente discriminabili e quantificabili, caratterizzati da magnitudo e velocità molto diverse tra loro. Tra le cause preponderanti che determinano l’ingressione marina possono essere individuati alcuni fenomeni naturali, climatici e geologici, i quali risultano fortemente influenzati dalle attività umane soprattutto a partire dal XX secolo. Tra questi si individuano: - la risalita del livello del mare, principalmente come conseguenza del superamento dell’ultimo acme glaciale e dello scioglimento delle grandi calotte continentali; - la subsidenza. Vaste porzioni delle piane costiere italiane risultano soggette a fenomeni di subsidenza. In certe zone questa assume proporzioni notevoli: per la fascia costiera emiliano-romagnola si registrano ratei compresi tra 1 e 3 cm/anno. Tale subsidenza è spesso il risultato della sovrapposizione tra fenomeni naturali (neotettonica, costipamento di sedimenti, ecc.) e fenomeni indotti dall’uomo (emungimenti delle falde idriche, sfruttamento di giacimenti metaniferi, escavazione di materiali per l’edilizia, ecc.); - terreni ad elevato contenuto organico: la presenza di depositi fortemente costipabili può causare la depressione del piano di campagna come conseguenza di abbassamenti del livello della falda superficiale (per drenaggi, opere di bonifica, emungimenti), dello sviluppo dei processi di ossidazione e decomposizione nei terreni stessi, del costipamento di questi sotto il proprio peso, della carenza di nuovi apporti solidi conseguente alla diminuita frequenza delle esondazioni dei corsi d’acqua; - morfologia: tra i fattori di rischio rientra l’assetto morfologico della piana e, in particolare il tipo di costa (lidi, spiagge, cordoni dunari in smantellamento, ecc. ), la presenza di aree depresse o comunque vicine al livello del mare (fino a 1-2 m s.l.m.), le caratteristiche dei fondali antistanti (batimetria, profilo trasversale, granulometria dei sedimenti, barre sommerse, assenza di barriere biologiche, ecc.); - stato della linea di costa in termini di processi erosivi dovuti ad attività umane (urbanizzazione del litorale, prelievo inerti, costruzione di barriere, ecc.) o alle dinamiche idro-sedimentarie naturali cui risulta soggetta (correnti litoranee, apporti di materiale, ecc. ). Scopo del presente studio è quello di valutare la probabilità di ingressione del mare nel tratto costiero emiliano-romagnolo del Lido delle Nazioni, la velocità di propagazione del fronte d’onda, facendo riferimento allo schema idraulico del crollo di una diga su letto asciutto (problema di Riemann) basato sul metodo delle caratteristiche, e di modellare la propagazione dell’inondazione nell’entroterra, conseguente all’innalzamento del medio mare . Per simulare tale processo è stato utilizzato il complesso codice di calcolo bidimensionale Mike 21. La fase iniziale di tale lavoro ha comportato la raccolta ed elaborazione mediante sistema Arcgis dei dati LIDAR ed idrografici multibeam , grazie ai quali si è provveduto a ricostruire la topo-batimetria di dettaglio della zona esaminata. Nel primo capitolo è stato sviluppato il problema del cambiamento climatico globale in atto e della conseguente variazione del livello marino che, secondo quanto riportato dall’IPCC nel rapporto del 2007, dovrebbe aumentare al 2100 mediamente tra i 28 ed i 43 cm. Nel secondo e terzo capitolo è stata effettuata un’analisi bibliografica delle metodologie per la modellazione della propagazione delle onde a fronte ripido con particolare attenzione ai fenomeni di breaching delle difese rigide ed ambientali. Sono state studiate le fenomenologie che possono inficiare la stabilità dei rilevati arginali, realizzati sia in corrispondenza dei corsi d’acqua, sia in corrispondenza del mare, a discapito della protezione idraulica del territorio ovvero dell’incolumità fisica dell’uomo e dei territori in cui esso vive e produce. In un rilevato arginale, quale che sia la causa innescante la formazione di breccia, la generazione di un’onda di piena conseguente la rottura è sempre determinata da un’azione erosiva (seepage o overtopping) esercitata dall’acqua sui materiali sciolti costituenti il corpo del rilevato. Perciò gran parte dello studio in materia di brecce arginali è incentrato sulla ricostruzione di siffatti eventi di rottura. Nel quarto capitolo è stata calcolata la probabilità, in 5 anni, di avere un allagamento nella zona di interesse e la velocità di propagazione del fronte d’onda. Inoltre è stata effettuata un’analisi delle condizioni meteo marine attuali (clima ondoso, livelli del mare e correnti) al largo della costa emiliano-romagnola, le cui problematiche e linee di intervento per la difesa sono descritte nel quinto capitolo, con particolare riferimento alla costa ferrarese, oggetto negli ultimi anni di continui interventi antropici. Introdotto il sistema Gis e le sue caratteristiche, si è passati a descrivere le varie fasi che hanno permesso di avere in output il file delle coordinate x, y, z dei punti significativi della costa, indispensabili al fine della simulazione Mike 21, le cui proprietà sono sviluppate nel sesto capitolo.

Bioremediation of PAHs - Limitations and soultions

Introduction 1.1 Occurrence of polycyclic aromatic hydrocarbons (PAH) in the environment Worldwide industrial and agricultural developments have released a large number of natural and synthetic hazardous compounds into the environment due to careless waste disposal, illegal waste dumping and accidental spills. As a result, there are numerous sites in the world that require cleanup of soils and groundwater. Polycyclic aromatic hydrocarbons (PAHs) are one of the major groups of these contaminants (Da Silva et al., 2003). PAHs constitute a diverse class of organic compounds consisting of two or more aromatic rings with various structural configurations (Prabhu and Phale, 2003). Being a derivative of benzene, PAHs are thermodynamically stable. In addition, these chemicals tend to adhere to particle surfaces, such as soils, because of their low water solubility and strong hydrophobicity, and this results in greater persistence under natural conditions. This persistence coupled with their potential carcinogenicity makes PAHs problematic environmental contaminants (Cerniglia, 1992; Sutherland, 1992). PAHs are widely found in high concentrations at many industrial sites, particularly those associated with petroleum, gas production and wood preserving industries (Wilson and Jones, 1993). 1.2 Remediation technologies Conventional techniques used for the remediation of soil polluted with organic contaminants include excavation of the contaminated soil and disposal to a landfill or capping - containment - of the contaminated areas of a site. These methods have some drawbacks. The first method simply moves the contamination elsewhere and may create significant risks in the excavation, handling and transport of hazardous material. Additionally, it is very difficult and increasingly expensive to find new landfill sites for the final disposal of the material. The cap and containment method is only an interim solution since the contamination remains on site, requiring monitoring and maintenance of the isolation barriers long into the future, with all the associated costs and potential liability. A better approach than these traditional methods is to completely destroy the pollutants, if possible, or transform them into harmless substances. Some technologies that have been used are high-temperature incineration and various types of chemical decomposition (for example, base-catalyzed dechlorination, UV oxidation). However, these methods have significant disadvantages, principally their technological complexity, high cost , and the lack of public acceptance. Bioremediation, on the contrast, is a promising option for the complete removal and destruction of contaminants. 1.3 Bioremediation of PAH contaminated soil & groundwater Bioremediation is the use of living organisms, primarily microorganisms, to degrade or detoxify hazardous wastes into harmless substances such as carbon dioxide, water and cell biomass Most PAHs are biodegradable unter natural conditions (Da Silva et al., 2003; Meysami and Baheri, 2003) and bioremediation for cleanup of PAH wastes has been extensively studied at both laboratory and commercial levels- It has been implemented at a number of contaminated sites, including the cleanup of the Exxon Valdez oil spill in Prince William Sound, Alaska in 1989, the Mega Borg spill off the Texas coast in 1990 and the Burgan Oil Field, Kuwait in 1994 (Purwaningsih, 2002). Different strategies for PAH bioremediation, such as in situ , ex situ or on site bioremediation were developed in recent years. In situ bioremediation is a technique that is applied to soil and groundwater at the site without removing the contaminated soil or groundwater, based on the provision of optimum conditions for microbiological contaminant breakdown.. Ex situ bioremediation of PAHs, on the other hand, is a technique applied to soil and groundwater which has been removed from the site via excavation (soil) or pumping (water). Hazardous contaminants are converted in controlled bioreactors into harmless compounds in an efficient manner. 1.4 Bioavailability of PAH in the subsurface Frequently, PAH contamination in the environment is occurs as contaminants that are sorbed onto soilparticles rather than in phase (NAPL, non aqueous phase liquids). It is known that the biodegradation rate of most PAHs sorbed onto soil is far lower than rates measured in solution cultures of microorganisms with pure solid pollutants (Alexander and Scow, 1989; Hamaker, 1972). It is generally believed that only that fraction of PAHs dissolved in the solution can be metabolized by microorganisms in soil. The amount of contaminant that can be readily taken up and degraded by microorganisms is defined as bioavailability (Bosma et al., 1997; Maier, 2000). Two phenomena have been suggested to cause the low bioavailability of PAHs in soil (Danielsson, 2000). The first one is strong adsorption of the contaminants to the soil constituents which then leads to very slow release rates of contaminants to the aqueous phase. Sorption is often well correlated with soil organic matter content (Means, 1980) and significantly reduces biodegradation (Manilal and Alexander, 1991). The second phenomenon is slow mass transfer of pollutants, such as pore diffusion in the soil aggregates or diffusion in the organic matter in the soil. The complex set of these physical, chemical and biological processes is schematically illustrated in Figure 1. As shown in Figure 1, biodegradation processes are taking place in the soil solution while diffusion processes occur in the narrow pores in and between soil aggregates (Danielsson, 2000). Seemingly contradictory studies can be found in the literature that indicate the rate and final extent of metabolism may be either lower or higher for sorbed PAHs by soil than those for pure PAHs (Van Loosdrecht et al., 1990). These contrasting results demonstrate that the bioavailability of organic contaminants sorbed onto soil is far from being well understood. Besides bioavailability, there are several other factors influencing the rate and extent of biodegradation of PAHs in soil including microbial population characteristics, physical and chemical properties of PAHs and environmental factors (temperature, moisture, pH, degree of contamination). Figure 1: Schematic diagram showing possible rate-limiting processes during bioremediation of hydrophobic organic contaminants in a contaminated soil-water system (not to scale) (Danielsson, 2000). 1.5 Increasing the bioavailability of PAH in soil Attempts to improve the biodegradation of PAHs in soil by increasing their bioavailability include the use of surfactants , solvents or solubility enhancers.. However, introduction of synthetic surfactant may result in the addition of one more pollutant. (Wang and Brusseau, 1993).A study conducted by Mulder et al. showed that the introduction of hydropropyl-ß-cyclodextrin (HPCD), a well-known PAH solubility enhancer, significantly increased the solubilization of PAHs although it did not improve the biodegradation rate of PAHs (Mulder et al., 1998), indicating that further research is required in order to develop a feasible and efficient remediation method. Enhancing the extent of PAHs mass transfer from the soil phase to the liquid might prove an efficient and environmentally low-risk alternative way of addressing the problem of slow PAH biodegradation in soil.

Studio del processo produttivo del riciclo di materiali provenienti da attività di C&D in un impianto di nuova realizzazione

Lo studio del processo produttivo del riciclo di materiali provenienti da attività di C&D in un impianto di nuova realizzazione, presentato in questa tesi di laurea,è così articolato: nel primo capitolo si analizza la complicata evoluzione della normativa in materia di rifiuti (non solo da C&D) su scala europea e nazionale accennando i provvedimenti legislativi su scala regionale, con particolare riferimento alla Regione Veneto. Si esamineranno, pertanto, le direttive e le decisioni della Comunità Europea che hanno ispirato, a partire dal 1975, i provvedimenti legislativi nazionali, tra cui vale la pena di ricordare il “Decreto Ronchi”, emanato nel febbraio del 1997, l’attuale D.Lgs. 3/4/2006 n.152, e i Decreti Ministeriali di riferimento per la materia di studio, ovvero il D.M. 5/2/1998, riguardante l’individuazione dei rifiuti per cui è possibile procedere al loro trattamento in regime semplificato e l’ancora poco attuato D.M.8/5/2003 n.203, riferito all’utilizzo di materiale riciclato nelle Pubbliche Amministrazioni. Il secondo capitolo definisce, invece, le caratteristiche principali dei rifiuti da C&D, appartenenti alla categoria dei rifiuti inerti, e delinea le odierne problematiche inerenti a tali materiali. A conferma di queste, nella seconda parte del capitolo, sono presentati alcuni dati che fotografano oggettivamente gli scenari attuali in Europa e in Italia in riferimento alla produzione, al recupero e allo smaltimento di questa categoria di rifiuti. In seguito, il terzo capitolo inizia a definire gli aspetti relativi alla realizzazione di un impianto di studio per il riciclo di rifiuti da C&D. In esso si evidenziano le procedure amministrative, gli adempimenti burocratici e in generale tutti gli aspetti inerenti alla gestione dei rifiuti da C&D per l’esecuzione delle attività di recupero e smaltimento previste dal D.Lgs. n.152/2006, così come modificato dal recentissimo D.Lgs. n.4/2008. Il quarto capitolo definisce i termini per poter considerare i rifiuti da C&D trattati in impianto come MPS. L’attenzione è riposta sulla Direttiva 89/106/CEE, che impone obbligatoriamente, dal 01/06/2004, la marcatura CE per tutti i prodotti da costruzione e, quindi, anche per gli aggregati riciclati. Pertanto, in questo capitolo, vengono definite le prove richieste obbligatoriamente dal D.M 11/4/2007 in accordo con la norma europea UNI EN 13242 recante “Aggregati per materiali non legati e legati con leganti idraulici per l'impiego in opere di ingegneria civile e nella costruzione di strade" ed, in conclusione, viene studiata la Circolare n.5205/2005 che dovrebbe dare attuazione nel settore edile, stradale e ambientale al D.M. n.203/2003. Successivamente, il quinto capitolo delinea le caratteristiche principali degli impianti di trattamento per il recupero dei rifiuti da C&D, delineando le principali differenze tra gli impianti fissi e i mobili ed esaminando le diverse fasi del ciclo produttivo, anche in relazione ad un impianto di studio situato nella provincia di Verona. Infine, il sesto capitolo riassume i risultati delle prove di marcatura CE per gli aggregati riciclati prodotti nell’impianto descritto. Tali prove sono state eseguite presso il Laboratorio di Strade della Facoltà di Ingegneria dell’Università degli Studi di Bologna.

Untersuchungen von intrazellulären Signalwegen bei neuraler Determinierung und Differenzierung in vitro: Einfluß von GAP-43 und Bcl-2

Die PCC7-Mz1-Zellinie stellt ein geeignetes Modell dar, um frühe neurale Determinierungs- und Differenzierungsprozesse unter kontrollierten Bedingungen in vitro zu untersuchen. Aus pluripotenten Stammzellen entwickelt sich nach Behandlung mit dem Morphogen Retinsäure (RA) ein stabiles Muster aus Neuronen, Fibroblasten und Astroglia-Zellen. Parallel stirbt ein reproduzierbarer Anteil der Kultur apoptotisch. Zur näheren Aufklärung der molekularen Vorgänge während der neuralen Entwicklung wurde der Einfluß von zwei Schlüsselmolekülen - dem Proteinkinase C Substrat (PKC) GAP-43 sowie dem antiapoptotischen Bcl-2 Protein - auf die neurale Differenzierung und die damit assoziierten Apoptoseereignisse der PCC7-Mz1-Zellen untersucht. Dazu wurden stabile Zellinien, die eine Überexpression von GAP-43 bzw. von Bcl-2 aufwiesen, hergestellt. GAP-43In PCC7-Mz1-Zellen wurde die Expression von GAP-43 sowohl auf mRNA- als auch auf Protein-Ebene innerhalb von 24 Stunden nach Zugabe von RA hochreguliert. GAP-43 war bereits in noch proliferierenden neuronalen Vorläuferzellen als Substrat für PKC und als Interaktionspartner von Calmodulin funktionell. Die Überexpression von GAP-43 in PCC7-Mz1-Zellen förderte die Ausprägung des neuronalen Phänotyps. Das Differenzierungspotential der Mz-GAP-43 Klone war eingeschränkt, da sich nach Induktion mit RA aus den Stammzellen nur noch Neurone, aber keine Fibroblasten und Astroglia-Zellen mehr entwickelten. Die Determinierung für das neuronale Entwicklungsschicksal war in den Mz-GAP-43 Klonen stärker fortgeschritten als in MzN-Klonen, die durch Subklonierung aus PCC7-Mz1-Zellen generiert wurden, da die GAP-43 überexprimierenden Zellen durch Wachstum auf Laminin nicht in den pluripotenten Phänotyp revertiert werden konnten. Aufgrund der Interaktion zwischen GAP-43 und Calmodulin in Stammzellen der Mz-GAP-43 Klone kann man vermuten, daß die neuronalen Determinierungsprozesse über Ca2+/Calmodulin-abhängige Signalwege verlaufen. Da das Gen für den Transkriptionsfaktor NCNF (