Comparison of Trehalose/Hyaluronic Acid (HA) vs. 0.001% Hydrocortisone/HA Eyedrops on Signs and Inflammatory Markers in a Desiccating Model of Dry Eye Disease (DED)

Background: Dry eye disease (DED) is a multifactorial disease where ocular surface inflammation and damage play key etiological roles. Purpose: To compare a combination of 3% trehalose (T) and 0.15% hyaluronic acid (HA) (Thealoz duo(R), T/HA) with a tear substitute containing 0.001% hydrocortisone (I) and 0.2% HA (Idroflog(R), I/HA), with respect to changes on signs and inflammatory markers in a mouse DED model. Methods: Thirty 12-week-old C57BL/6 mice were exposed in a controlled-environment chamber as a desiccating stress model of DED for 35 days. At day 14 (T1), administration of 5 mu L T or I in the right eye (RE) or NaCl 0.9% in the left eye (LE) started, twice a day. Animals were sacrificed after 7 (T2), 14 (T3), 21 (T4, endpoint) days from the beginning of treatment. Corneal fluorescein staining ratio (Image J), histological and histochemical assessment of ocular surface tissues (goblet cell GC density and characterization -PAS, Alcian blue pH 2.5, pH 1.0, and MUC4 expression-in the superior and inferior conjunctiva), and levels of inflammatory markers HLA-DR, IL-1 beta and TNF-alpha in cornea and conjunctiva were measured. Results: No animal fully recovered from DED signs at the endpoint. Difference between arms was observed at T3 and T4, with T treated eyes showing a higher corneal damage reduction, PAS-positive GC recovery, lower inflammatory marker expression as compared to the I treated ones. Conclusions: Data suggest that 21 days of treatment with T/HA improved signs, GC recovery and inflammatory markers in a DED mouse model, to a greater extent as compared to I/HA. Data suggest that 21 days of treatment with T/HA improved signs, GC recovery and inflammatory markers in a DED mouse model, to a greater extent as compared to I/HA

Photobiomodulation at Defined Wavelengths Regulates Mitochondrial Membrane Potential and Redox Balance in Skin Fibroblasts

Starting from the discovery of phototherapy in the beginning of the last century, photobiomodulation (PBM) has been defined in late 1960s and, since then, widely described in different in vitro models. Robust evidence indicates that the effect of light exposure on the oxidative state of the cells and on mitochondrial dynamics, suggesting a great therapeutic potential. The translational scale-up of PBM, however, has often given contrasting and confusing results, mainly due to light exposure protocols which fail to adequately control or define factors such as emitting device features, emitted light characteristics, exposure time, cell target, and readouts. In this in vitro study, we describe the effects of a strictly controlled light-emitting diode (LED)-based PBM protocol on human fibroblasts, one of the main cells involved in skin care, regeneration, and repair. We used six emitter probes at different wavelengths (440, 525, 645, 660, 780, and 900 nm) with the same irradiance value of 0.1 mW/cm2, evenly distributed over the entire surface of the cell culture well. The PBM was analyzed by three main readouts: (i) mitochondrial potential (MitoTracker Orange staining), (ii) reactive oxygen species (ROS) production (CellROX staining); and (iii) cell death (nuclear morphology). The assay was also implemented by cell-based high-content screening technology, further increasing the reliability of the data. Different exposure protocols were also tested (one, two, or three subsequent 20 s pulsed exposures at 24 hr intervals), and the 645 nm wavelength and single exposure chosen as the most efficient protocol based on the mitochondrial potential readout, further confirmed by mitochondrial fusion quantification. This protocol was then tested for its potential to prevent H2O2-induced oxidative stress, including modulation of the light wave frequency. Finally, we demonstrated that the controlled PBM induced by the LED light exposure generates a preconditioning stimulation of the mitochondrial potential, which protects the cell from oxidative stress damage

Neuroprotection and neuroregeneration: roles for the white matter

Efficient strategies for neuroprotection and repair are still an unmet medical need for neurodegenerative diseases and lesions of the central nervous system. Over the last few decades, a great deal of attention has been focused on white matter as a potential therapeutic target, mainly due to the discovery of the oligodendrocyte precursor cells in the adult central nervous system, a cell type able to fully repair myelin damage, and to the development of advanced imaging techniques to visualize and measure white matter lesions. The combination of these two events has greatly increased the body of research into white matter alterations in central nervous system lesions and neurodegenerative diseases and has identified the oligodendrocyte precursor cell as a putative target for white matter lesion repair, thus indirectly contributing to neuroprotection. This review aims to discuss the potential of white matter as a therapeutic target for neuroprotection in lesions and diseases of the central nervous system. Pivot conditions are discussed, specifically multiple sclerosis as a white matter disease; spinal cord injury, the acute lesion of a central nervous system component where white matter prevails over the gray matter, and Alzheimer's disease, where the white matter was considered an ancillary component until recently. We first describe oligodendrocyte precursor cell biology and developmental myelination, and its regulation by thyroid hormones, then briefly describe white matter imaging techniques, which are providing information on white matter involvement in central nervous system lesions and degenerative diseases. Finally, we discuss pathological mechanisms which interfere with myelin repair in adulthood

Introduzione

Dal volume emerge quindi un quadro del mondo e delle relazioni finanziarie tra Italia e Svizzera definitivamente sottratto al luogo comune di paradiso fiscale, che ha finito per schiacciare sulla storia di qualche decennio del XX secolo la natura plurisecolare e composita \u2013 non limitatamente finanziaria ma commerciale e industriale di reciproco scambio \u2013 dei legami tra i due paesi. Due paesi separati geograficamente dalla catena alpina che di fatto non ha svolto il ruolo di barriera, ma di cerniera unificatrice, di canale attraverso cui uomini, culture e istituzioni si sono incontrate e contaminate, pur mantenendo la propria specificit\ue0 e contribuendo allo sviluppo economico di entrambe. In alcuni casi, come per il confine tra Lombardia e Canton Ticino, l\u2019appartenenza a domini territoriali differenti ha creato una sorta di \u201cmicroclima economico\u201d che ha prodotto condizioni favorevoli per le due aree fin dall\u2019et\ue0 moderna. Molto tempo prima che i capitali italiani venissero attratti oltre frontiera per motivi di sicurezza, riservatezza e vantaggio fiscale, dalla Svizzera prendevano la direzione inversa i flussi finanziari costituiti dalle eccedenze dei territori che \u201cesportavano\u201d mercenari nell\u2019Europa del XVI e del XVII secolo; mentre tutti gli altri stati del Continente imponevano tasse per pagare le soldatesche, la Svizzera delle repubbliche oligarchiche usufruiva infatti del loro pagamento e delle loro rimesse in entrata, rendendo inutile aggravare i carichi fiscali all\u2019interno e realizzando una sorta di paradiso fiscale nell\u2019epoca moderna . In entrambi, durante l\u2019et\ue0 preindustriale l\u2019attivit\ue0 creditizia appare cos\uec in parte dominata da una massa di persone, lontane dal mondo professionale, che alle volte finivano per alimentare le orbite finanziarie locali e internazionali o che spesso si muovevano in una zona grigia; ma sempre all\u2019interno di un \u201cmercato\u201d che allocava le risorse soprattutto sulla base delle informazioni, su chi aveva denaro, su chi ne richiedeva, su chi era un buon pagatore e su chi no, e in cui svolgevano un ruolo cardine, e tra loro concorrenziale, i notai e i sensali; figure che proprio nella gestione di questi meccanismi reputazionali trovavano gli incentivi microeconomici, in termini di conservazione e di incremento della clientela, che li spingevano a fornire referenze e a realizzare intermediazioni affidabili, con l\u2019effetto di abbassare i costi di transazione del mercato. Tra i territori di matrice cattolica all\u2019interno dei due paesi risaltano quindi numerose le analogie e le continuit\ue0 soprattutto nella presenza costante di un mercato del credito informale e capillare, in grado di operare con efficacia sia nei centri urbani che nelle aree rurali; mercato informale animato in particolare dall\u2019intervento dei corpi religiosi che accanto all\u2019opera spirituale svolgevano una sistematica attivit\ue0 di prestiti a interesse, reimmettendo in circolo il risparmio forzato costituito dalle doti, dai legati e dalle donazioni. In un momento in cui le banche (intese nel loro senso ottocentesco) non esistevano ancora, questa rete \u201cnon-istituzionalizzata\u201d del credito and\uf2 a sostegno, al di qua e al di l\ue0 delle Alpi, dei sistemi produttivi locali e della loro crescita. Ma ne esce confermata ed arricchita, anche per l\u2019epoca contemporanea, la biunivocit\ue0 degli scambi e la funzione di uomini e capitali italiani in Svizzera nella fase di fondazione delle prime banche in Ticino. Cos\uec come appare ribadito e significativo l\u2019apporto svolto dagli imprenditori elvetici, che insieme ai finanziamenti portarono con s\ue9 tecnologie in grado in alcuni casi \u2013 come nelle regioni settentrionali italiane \u2013 di sostenere un\u2019industria manifatturiera in espansione e in altri di attivarla \u2013 come nei paesi meridionali della Penisola \u2013 intervenendo in diversi settori manifatturieri, da quello tessile, a quello alimentare e della orologeria, oltre a quello finanziario. Del resto, come dimostra il saggio conclusivo su Il sistema bancario svizzero in evoluzione: tradizione e innovazione, sollecitato, dopo la conclusione del convegno, a Luisa Anderloni e Angelo Tasca, studiosi di finanza aziendale e di economia degli intermediari finanziari, il segreto bancario \u2013 il cui processo di revisione sta segnando, dopo un avvio che pareva inarrestabile, preoccupanti battute d\u2019arresto \u2013 costituisce s\uec un elemento critico e importante, ma non esaurisce certamente la forza competitiva e le peculiarit\ue0 della struttura creditizia elvetica. Sullo sfondo del trade-off fra liberismo e regolamentazione che ha caratterizzato il sistema in questi decenni, ne emerge infatti una notevole dinamica competitiva basata, sia sulla complementarit\ue0 tra sistema bancario e sistema assicurativo, sia sulla persistenza di un elevato grado di specializzazione funzionale tra banche regionali e casse di risparmio rispetto alle grandi banche universali. Un\u2018integrazione a cui si aggiunge un\u2019elevata attenzione del sistema finanziario verso i fenomeni pi\uf9 innovativi, quali lo sviluppo di realt\ue0 legate alla sfera del fintech ed un attivo processo di canalizzazione degli investimenti verso le piattaforme internet innovative (blockchain), declinate al fine di operare come sistemi di creazione di moneta digitale e di nuovi strumenti di pagamento

Banche e banchieri in Italia e in Svizzera : attività, istituzioni e dinamiche finanziarie tra 16. e 21. secolo

Sulla lunga storia dei rapporti finanziari tra Italia e Svizzera ha da sempre gettato la sua ombra il cosiddetto \uabsegreto bancario\ubb. L\u2019attenzione per il tema della riservatezza ha contribuito sia a schiacciare l\u2019analisi storica sui decenni pi\uf9 recenti, sia a cristallizzare un\u2019immagine stereotipata di questa relazione, che vedeva l\u2019Italia come serbatoio di capitali per la ricca e catafratta Confederazione elvetica. Obiettivo di questo volume \ue8 riportare alla realt\ue0 storica, fondata su ricerche e fonti archivistiche, la complessit\ue0 di questi rapporti animati da un fertile scambio di denaro, operatori, tecniche e know how tra le due nazioni. Si profilano quindi sia per l\u2019et\ue0 moderna che per l\u2019et\ue0 contemporanea un\u2019intensa reciprocit\ue0 di relazioni, una funzionale complementariet\ue0 dei flussi di finanziamento e molte analogie nella struttura dell\u2019offerta creditizia. Durante i secoli preindustriali i territori italiani ed elvetici, di matrice cattolica, appaiono accomunati dall\u2019attivit\ue0 di operatori \uabnon istituzionalizzati\ubb (come i notai o gli enti religiosi), che svilupparono un\u2019efficace rete di credito informale, in parte sovrapposta e concorrente alla diffusione delle nuove banche ottocentesche. Cos\uec anche durante l\u2019et\ue0 contemporanea, dove uomini e capitali continuano a muoversi tra i due paesi generando crescita, imprenditorialit\ue0 e innovazione. Un flusso di scambi e di contaminazioni che sembra continuare anche dopo l\u2019abbattimento del segreto bancario, a testimonianza delle radici e della tenuta della genealogia di questo rapporto

Physiochemical responses of Ailanthus altissima under the challenge of Verticillium dahliae: elucidating the decline of one of the world’s worst invasive alien plant species

Natural infections of Verticillium spp. (Fungi, Ascomycota) on Ailanthus altissima have suggested to consider the biological control as a promising strategy to counteract this invasive plant, which is otherwise difficult to control by traditional mechanical and chemical treatments. Verticillium wilt is able to lead plants to death, throughout a pathogenic mechanism including vessel occlusions and production of degrading enzymes and phytotoxins. In this study, a 10 weeks open air pot experiment was set to investigate the ecophysiological and biochemical responses of Ailanthus trees artificially inoculated in the trunk with the V. dahliae strain VdGL16, previously isolated in Central Italy from the same host. Inoculated plants showed visible injuries starting from 2 weeks post inoculation (wpi), that progressively developed until a final severe defoliation. The fungal infection rapidly compromised the plant water status, and photosynthesis was impaired due to both stomatal and mesophyll limitations from 4 wpi, with subsequent detrimental effects also on PSII activity. Moreover, the disease altered the translocations of nutrients, as confirmed by cation and carbohydrate contents, probably due to a consumption of simple sugars and starch reserves without replacement of new photosynthesized. An accumulation of osmolytes (abscisic acid and proline) and phenylalanine (a precursor of phenylpropanoids) was also reported at 8 wpi, this being a response mechanism that needs to be further elucidated. However, the activation delay of such defence strategy inevitably did not avoid the premature defoliation of plants and the decline of physiochemical parameters, confirming the key role of Verticillium in Ailanthus decay

In vitro exposure to very low-level laser modifies expression level of extracellular matrix protein RNAs and mitochondria dynamics in mouse embryonic fibroblasts

BACKGROUND: Low-level lasers working at 633 or 670 nm and emitting extremely low power densities (Ultra Low Level Lasers - ULLL) exert an overall effect of photobiostimulation on cellular metabolism and energy balance. In previous studies, it was demonstrated that ULLL pulsed emission mode regulates neurite elongation in vitro and exerts protective action against oxidative stress. METHODS: In this study the action of ULLL supplied in both pulsed and continuous mode vs continuous LLL on fibroblast cultures (Mouse Embryonic Fibroblast-MEF) was tested, focusing on mitochondria network and the expression level of mRNA encoding for proteins involved in the cell-matrix adhesion. RESULTS: It was shown that ULLL at 670 nm, at extremely low average power output (0.21 mW/ cm(2)) and dose (4.3 mJ/ cm(2)), when dispensed in pulsed mode (PW), but not in continuous mode (CW) supplied at both at very low (0.21 mW/cm(2)) and low levels (500 mW/cm(2)), modifies mitochondria network dynamics, as well as expression level of mRNA encoding for selective matrix proteins in MEF, e.g. collagen type 1α1 and integrin α5. CONCLUSIONS: We suggest that pulsatility, but not energy density, is crucial in regulating expression level of collagen I and integrin α5 in fibroblasts by ULLL

Efficiency and costs of the health management in an organic dairy farm where we use unconventional medicines

The EU organic regulation explicitly promote the use of unconventional therapies, like homoeopathy and phytotherapy. The aim of the present study was to investigate the efficiency and the costs of these treatment methods. From December 2006 to September 2008, we analyzed the data recorded in an organic dairy farm where the animals are normally treated by classical unicistic homeopathy and phytotherapy, and only when indispensable, by allophaty, antiparasitic drugs, surgery and vaccines. The use of homeopathy resulted to be predominant in comparison with the others treatments. Besides, our trial showed that homeopathy and phytotherapy could be used to treat, with good outcomes, the majority of diseases that occur in a dairy cattle farm, even if, sometimes, conventional medicines have to be used. The costs for unconventional treatments are very low in comparison with conventional ones. This will allow the spreading of unconventional medicines in the Italian organic farms

Oceanic giants in the Mediterranean: first mitochondrial analysis of leatherback turtles (Dermochelys coriacea) in the Adriatic and Tyrrhenian seas

The leatherback turtle Dermochelys coriacea (Vandelli, 1761) is an occasional trophic visitor of the Mediterranean basin. So far, very few individuals have been genetically analysed from this sea and none from Italy. We sequenced a mitochondrial DNA fragment of three specimens of D. coriacea found in recent years along the North-Adriatic and Tyrrhenian shores. They were all females approaching adult stage. Causes of death were attributable to the main threats for sea turtles in Mediterranean waters, all related to human activities (collisions with boats, entanglement in fishing nets and plastic debris ingestion). Two different mitochondrial haplotypes were observed, with the two North-Adriatic turtles sharing the same one. Compared to known Dermochelys sequences and previous genetic characterization of rookeries, these results suggest that the most probable origin of at least two of the three leatherbacks was the western Atlantic