Photodynamic therapy and adapalene in dermatology: synergistic effects in immortal human keratinocytes

We compared the effects of methyl levulinate (MAL)/photodynamic therapy (PDT) and adapalene, evaluated singly, versus combination therapy on HaCaT keratinocytes. Our aim was to determine whether the additive/synergistic outcomes of combination treatment were such that doses of each component could be reduced without affecting treatment efficacy. The analysis of data from specific PDT/adapalene combinations results indicating effects ranging from additive to clearly synergistic. We first evaluated the effects on cell viability, cell cycle and protein expression profiles of each individual treatment, then we tried to understand the reasons and the mechanisms whereby cells under combined treatment move more efficiently to death. Although we observed therapeutic strengthening by increasing either drug doses or light fluences, reinforcement was particularly marked in combinations in which PDT was predominant. Thus, if PDT is appropriately tuned, the dose of the drug can be reduced without compromising the therapeutic response. As both photodynamic therapy and adapalene have been and are therapeutic approaches to treat different dermatological pathologies such as acne, actinic keratosis etc., our data suggest that the adapalene-PDT combination may have important spin-off in clinical dermatology as a strategy to tackle this nasty condition

PharmaCare 2018

[Italiano]: Il farmaco, nella sua accezione più ampia e generale, può essere ritenuto un bene sociale, la cui valenza simbolica e curativa varia in relazione alla dimensione ambientale e culturale nel quale si inserisce. In tal senso, le prescrizioni farmaceutiche rappresentano un indicatore privilegiato per la conoscenza del sistema salute di un determinato territorio, poiché costituiscono un punto di intersezione ideale tra la prospettiva medica e quella di mercato. Siffatte considerazioni hanno sollecitato l’elaborazione di questo Report che si pone, come obiettivi dichiarati, quello di essere uno strumento utile alla pianificazione di interventi di sanità pubblica, quanto quello di svolgere analisi approfondite sulle caratteristiche dei soggetti che usano i farmaci e sulle modalità di trattamento degli stessi, permettendo studi di appropriatezza prescrittiva su specifiche aree di rilevanza clinica e su specifiche coorti di soggetti. “PharmaCaRe Report 2018” è stato realizzato dal CIRFF (Centro Interdipartimentale di Ricerca in Farmacoeconomia e Farmacoutilizzazione) dell’Università degli Studi di Napoli Federico II, in collaborazione con la Direzione Generale della Tutela della Salute della Regione Campania, per delineare un quadro dettagliato circa il consumo e la prescrizione dei farmaci in Campania nel 2018. Questo Report intende infatti fornire una fotografia dettagliata dell’utilizzo che, in Campania, viene fatto dei farmaci in termini di spesa, volumi e tipologia. Le analisi dei dati prodotte offrono spunti importanti per correlare la prevalenza delle patologie nel territorio con il corrispondente utilizzo dei farmaci e suggeriscono un’interpretazione dei principali fattori che influenzano la variabilità nella prescrizione. La disponibilità di una banca dati che copre una popolazione assistibile di circa sei milioni di abitanti è d’altronde un potente strumento di ricerca per studiare gli effetti dell’utilizzo dei farmaci in condizioni di Real-World. La conoscenza delle dinamiche prescrittive, in termini qualitativi (appropriatezza d’uso), oltre che quantitativi (volumi di utilizzo) è la condizione necessaria per inquadrare in un contesto razionale la politica del farmaco, anche sotto il profilo della valutazione degli effetti degli interventi che il mercato, le normative o la cultura del farmaco sviluppano nel tempo. Per tali ragioni, “PharmaCaRe Report 2018” rappresenta un utile quanto prezioso supporto ai decisori per individuare strategie volte a ottimizzare l’allocazione delle risorse, nonché migliorare i percorsi di cura attraverso un monitoraggio costante, la promozione di più elevati standard di cura e l’uso sicuro, efficiente ed efficace dei farmaci ./[English]: In its broadest and most general sense, the drug can be considered a public resource, whose symbolic and curative value varies in relation to the environmental and cultural dimension in which it is embedded. In this sense, pharmaceutical prescriptions represent a privileged indicator for the knowledge of the health system of a given territory, since they constitute an ideal intersection point between the medical and the market perspective. Such considerations prompted the preparation of this Report. “PharmaCaRe Report 2018” has been produced by CIRFF (Centro Interdipartimentale di Ricerca in Farmacoeconomia e Farmacoutilizzazione) of the Federico II University of Naples, in collaboration with the Directorate-General for Health Protection of the Campania Region, to provide a detailed overview of the pharmaceutical consumption and prescriptions in Campania in 2018. This Report aims to provide a detailed picture of the use of medicines in the general population in Campania, in terms of expenditure, volumes and type. The analyses of the data produced offer important clues for correlating the prevalence of diseases in this area with the respective use of medicines and suggest an interpretation of the main factors influencing prescriptions' variability. The availability of a database covering a patient population of around six million is a powerful research tool for studying the effects of drug use in Real-World conditions. Knowledge of the dynamics of prescription, in qualitative terms (appropriateness of use), as well as quantitative (volumes of use) is the necessary condition to frame the drug policy in a rational context, also in terms of evaluating the effects of the interventions that the market, regulations or drug culture develop over time. For these reasons, “PharmaCaRe Report 2018” represents a useful and valuable tool for political decision-makers in identifying strategies aimed at optimizing the allocation of resources, as well as improving care pathways through constant monitoring, the promotion of higher standards of care and safe, efficient and effective use of drugs

Innovative approaches to active and healthy ageing: Campania experience to improve the adoption of innovative good practices

The demographic projections on the European population predict that people aged over 60 will increase by about two million/year in the next decades. Since 2012, the Campania Reference Site of the European Innovation Partnership on Active and Healthy Ageing supports the innovation of the Regional Health System, to face up demographic changes and sustainability. Campania Reference Site provides the opportunity to connect loco-regional stakeholders in social and health care services (universities, healthcare providers, social services, local communities and municipalities), with international organizations, in order to adopt and scale up innovative solutions and approaches. This paper describes the building process of Campania Reference Site and the main results achieved, that have been allowing it to become a hub for open innovation in the field of active and healthy aging at regional, national and international level

Combined therapy with delta-aminolevulinic acid/photodynamic therapy and EGF-R inhibitor Gefitinib in non small cell lung carcinoma cell lines

Non-small-cell lung cancer (NSCLC), accounts for approximately 80% of all lung tumors, that are a leading cause of cancer-related mortality in the world. Several protocols of monotherapy have been attempted with some success in a limited number and selected cases with several delusion and even failures. Combination therapy, may present some advantages and should be considered as a potentially promising approach. Although it has been proposed in certain conditions, yet it has not fully exploited. We have conducted an in vitro study on two non small cell lung carcinoma cell lines, namely A549 and H1299, that differ for the status of p53 protein (wid type and null respectively). We proposed a therapeutic approach based on the combination of anti EGFR drug (Gefitinib) and PDT (ALA-PDT). The combination is potentially efficient since the drug and PDT appear to target different cell growth pathways. The occurrence of simultaneous damages to different sites may improve the efficiency in killing the target cells. Gefitinib, is a synthetic EGF receptor inhibitor that blocks EGFR signal transduction pathways, responsible of the promotion of cancer cell proliferation. Photodynamic therapy (PDT) is a cancer treatment whose principal cytotoxicity is mediated by the production of reactive oxygen species that efficiently damage sub-cellular components. We demonstrated that specific combinations of Gefitinib and PDT treatment exert synergistic effect on cell growth inhibition of A549 and H1299 cells, and above all it strongly deranges the mitochondrial activity and cell proliferation. Interesting enough, such combinations contained Gefitinib at concentrations below the canonical effective value, so that the possible noxious side effects associated with the drug can be minimized. Having analyzed several molecular pathways upon individual and combined treatments, we observed that the two cell lines respond not identically at molecular levels especially as cell cycle and nuclear involvement are concerned. In particular PDT treatment induced S-phase block in H1299 and DNA damage. The latter observation was strengthened by the activation of damage sensor-proteins (ATM, ATR) plus the recruitment of histone H2AX. A549 cells did not perform similarly. Tentatively, this different behaviuor can be ascribed to the different status of the p53 protein in the two cell lines. In contrast, the behaviour of NF-B pathway, does not significantly differ in both cell lines. In fact the activation of NF-B transcription factor activity did not change following treatment with Gefitinib, was slight reduced following PDT, while in combined conditions a significant reduction in NF-B was observed. This decrease was determined by the the PDT-mediated inhibition of the proteasome, another recognized target in cancer therapy. In our systems we observed that the proteasome inhibition was primarily caused by PDT treatment, but it was efficiently sustained by Gefitinib. This fact explains the efficiency of the combined therapy

L’astrofisica per insegnare la fisica di base e la fisica moderna: l’esperienza dell’Università Roma Tre

A partire dal 2010 le Indicazioni Nazionali hanno introdotto l’insegnamento della fisica moderna nelle Scuole Secondarie Superiori. Le Università e gli enti di ricerca devono quindi supportare i docenti nel loro sforzo di trattare questi argomenti avanzati in classe, proponendo il più possibile attività interattive e approcci originali. In questo documento è presentato un esempio di trattazione della fisica moderna attraverso l’astrofisica e la cosmologia. Le attività sono state proposte e testate durante il Corso di Aggiornamento in presenza dell’Università Roma Tre, con l’idea che esse possano poi essere applicate anche ad un Corso di Formazione iniziale

Sperimentare la gravità con il telo elastico: linee guida e trucchi-Experience gravity with the rubber sheet: guidelines and tricks

Questo libro raccoglie schede operative, frutto di un lungo confronto con docenti, che guidano, attraverso consigli pratici, immagini, video e approfondimenti, il professore di scuola secondaria superiore nella realizzazione di attività sulla gravità utilizzando un telo elastico. Sono descritti i materiali e il procedimento necessari a costruire la struttura economica da usare in classe e il docente è accompagnato nella trattazione dei temi, dalle leggi di Keplero ai buchi neri.This book collects a series of educational cards, coming from a long discussion with teachers, that guide, through practical advice, images, videos and insights, the high school professor in the realization of different activities concerning gravity using a rubber sheet. The materials and the procedure necessary to build the economic structure to be used in the classroom are described; the teacher is then accompanied in the discussion of the topics: from Kepler's laws to black holes

Introducing General Relativity in High School: A Guide for Teachers

Introducing Modern Physics represents an increasingly urgent need, towards which physics education concentrates many efforts. In order to contribute to this attempt, at the Department of Mathematics and Physics of Roma Tre University in Rome we focused on the possibility of treating General Relativity (GR) at high school level. We started with an interactive activity addressed to students that exploits the rubber sheet analogy (RSA) to show various phenomena related to gravity using the concept of space-time. Then, having verified its effectiveness, we began to include it among the initiatives the Department carry for high school teacher professional development, with the explicit aim of making them capable of carrying on the activity autonomously in the classrooms. In this paper, we analyse the teacher training approach we realized, and all the materials developed

Twilight effects of low doses of ionizing radiation on cellular systems: a bird's eye view on current concepts and research.

The debate about the health risks from low doses of radiation is vigorous and often acrimonious since many years and does not appear to weaken. Being far from completeness, this review presents only a bird's eye view on current concepts and research in the field. It is organized and divided in two parts. The first is dedicated to molecular responses determined by radiation-induced DNA ruptures. It focuses its attention on molecular pathways that are activated by ATM and tries to describe the variegated functions and specific roles of Chk2 and p53 and other proteins in sensing, promoting and executing DNA repair. The second part is more concerned with the risk associated with exposure to low dose radiation and possible effects that the radiation-affected cell may undergo. These effects include induction of apoptosis and mitotic catastrophe, bystander effect and genomic instability, senescence and hormetic response. Current hypotheses and research on these issues are briefly discussed

Enhancing Photodynamyc Therapy Efficacy by Combination Therapy: Dated, Current and Oncoming Strategies

Combination therapy is a common practice in many medical disciplines. It is defined as the use of more than one drug to treat the same disease. Sometimes this expression describes the simultaneous use of therapeutic approaches that target different cellular/molecular pathways, increasing the chances of killing the diseased cell. This short review is concerned with therapeutic combinations in which PDT (Photodynamyc Therapy) is the core therapeutic partner. Besides the description of the principal methods used to assess the efficacy attained by combinations in respect to monotherapy, this review describes experimental results in which PDT was combined with conventional drugs in different experimental conditions. This inventory is far from exhaustive, as the number of photosensitizers used in combination with different drugs is very large. Reports cited in this work have been selected because considered representative. The combinations we have reviewed include the association of PDT with anti-oxidants, chemotherapeutics, drugs targeting topoisomerases I and II, antimetabolites and others. Some paragraphs are dedicated to PDT and immuno-modulation, others to associations of PDT with angiogenesis inhibitors, receptor inhibitors, radiotherapy and more. Finally, a look is dedicated to combinations involving the use of natural compounds and, as new entries, drugs that act as proteasome inhibitors