721 research outputs found

    The Eocene unconformity of the Briançonnais domain in the French—Italian Alps, revisited (Marguareis massif, Cuneo); a hint for a Late Cretaceous—Middle Eocene frontal bulge setting

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    The tectonic significance of the Eocene unconformity in the Brianconnais domain, classically regarded as recording a compressional event, is re-evaluated, based on field studies in the Marguareis m..

    Propolis induces AQP3 expression: A possible way of action in wound healing

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    Propolis is the generic name of a complex of resinous compound collected by honeybees and it has been utilized for many years in folk medicine. As other products generated by honeybees (such as royal jelly, pollen, honey), propolis has great therapeutic properties, but very little scientific information is available. Therefore, this study was aimed at exploring the potential wound healing properties of propolis. To that end, we utilized an in vitro scratch wound healing model consisting of human immortalized keratinocytes. Our scratch wound data clearly demonstrated that propolis induced a pronounced increase in the wound repair abilities of keratinocytes. A cell migration assay showed that propolis stimulated keratinocytes to close the wound. We revealed the role of H2O2 as the main mediator of propolis regenerative properties. We showed that this extracellularly released H2O2 could pass across the plasma membrane through a specific aquaporin (i.e., AQP3) modulating intracellular responses. The data offer a biological characterization of propolis positive effects suggesting that propolis could also be utilized in wound treatment within clinical settings

    Alpine tectonic evolution and thermal water circulations of the Argentera Massif (South-Western Alps)

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    Three groups of thermal springs with temperatures close to 70 °c discharge both in the core (at bagni di Vinadio and terme di Valdieri) and on the external margin (at Berthemont-Les-Bains) of the Argentera Massif. Detailed structural field analysis carried out on the hydrothermal sites allows us to delineate both a model of Alpine tectonic evolution of the Argentera Massif and the patterns of hydrothermal circulation that were active during its final exhumation. the observed fault rock assemblages provide information relative to deformation that occurred in viscous, frictional-to-viscous and frictional crustal regimes. During the Early Miocene, the bersezio Fault Zone and the Fremamorta shear Zone, two main mylonitic shear zones, mainly accommodated regional transpression and provided pathways for fluid flow promoting mineral reactions in greenschist facies. During the Late Miocene-Early Pliocene, frictional-to-viscous deformation affected the massif, which underwent predominant transpression in the internal sectors and extension on the external margin. During the Plio-Pleistocene, deformation in frictional condition accompanied the final exhumation of the massif in a transpressive regime and resulted in the development of the NW-SE striking cataclastic zones. The hydraulic properties of these structures mainly influence the patterns of the active thermal circulations and the localization of the recharge and discharge zones. At Berthemont these faults represent conduits, whereas at Vinadio and Valdieri they form complex systems of conduits and barriers. In these two latter sites, the cataclastic faults compose flower structures that constrain laterally the thermal fluid flows while intensely fractured granites sited at depth constitute a highly-transmissive geothermal reservoir. Less permeable migmatitic gneisses overlaying the granites prevent a massive infiltration of the cold fluids at depth. This context favours within the high-ermeability fractures granites the development of buoyancy-driven flows which combined with topographically-driven flows, provided the conditions for the pflow of the high-temperature waters. © Birkhäuser Verlag, Basel, 2009

    The “Eyeballing” technique : an emerging and alerting trend of alcohol misuse

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    Alternative methods of alcohol consumption have recently emerged among adolescents and young adults, including the alcohol “eyeballing”, which consist in the direct pouring of alcoholic substances on the ocular surface epithelium. In a context of drug and behavioural addictions change, “eyeballing” can be seen as one of the latest and potentially highly risky new trends. We aimed to analyze the existing medical literature as well as online material on this emerging trend of alcohol misusePeer reviewedFinal Published versio

    Genomic organization and cytokine-mediated inducibility of the human TRIM-8/Gerp gene.

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    Cytokine signaling is negatively regulated by a set of SH2 domain-containing proteins, the Suppressors of Cytokine Signaling (SOCS) acting as intracellular modulators. Experimental evidence indicates that SOCS gene expression is induced by cytokines and pro-inflammatory stimuli and is highly controlled both at transcription and translation level. Furthermore, SOCS proteins appear rapidly degraded inside the cells, mostly controlling their stability by interacting with specific molecules such as elongin B and C. It has been shown that SOCS-1/JAB, a member of the SOCS family, interacts with TRIM-8/Gerp, a new ring protein specifically binding SOCS-1 recombinant polypeptide in-vitro and in-vivo. Trim-8/Gerp, transcribes a 3.0-kb mRNA, spans 551 AA and is highly conserved during evolution. In addition, it can be induced by IFN-Îł in epithelial and lymphoid cells and is expressed mostly ubiquitously in murine and human tissues. Here in this report we present the genomic organization of this new SOCS-1 interactor, and we add new tools for extending investigation of the complex mechanism that undergoes negatively regulation of cytokine signaling

    The FDA “black box” warning on antidepressant suicide risk in young adults: More harm than benefits?

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    The decision made in the year 2004 by the U.S. Food and Drug Administration (FDA) to require a boxed warning on antidepressants regarding the risk of suicidality in young adults still represents a matter of controversy. The FDA warning was grounded on industry-sponsored trials carried one decade ago or earlier. However, within the past decade, an increasing number of reports have questioned the actual validity of the FDA warning, especially considering a decline in the prescription of the antidepressant drugs associated with an increase in the rate of suicidal events among people with severe depression. The present report provides an overview of the FDA black box warning, also documenting two Major Depressive Disorder patients whose refusal to undergo a pharmacological antidepressant treatment possibly led to an increased risk for suicidal behaviors. The concerns raised by the FDA black box warning need to be considered in real-world clinical practice, stating the associated clinical and public health implications

    The diffusion of Performance and Image Enhancing Drugs (PIEDs) on the internet : The abuse of the cognitive enhancer Piracetam

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    This is an Accepted Manuscript of an article published by Taylor & Francis in Substance Use & Miuse on December 2014, available online at: https://doi.org/10.3109/10826084.2014.912232Introduction: Performance and image-enhancing drugs (PIEDs), also known as “lifestyle drugs,” are increasingly sold on the Internet to enhance cognitive as well as sexual, muscular, attentive, and other natural capacities. Our analysis focuses on the misuse of the cognitive enhancer piracetam. Methods: A literature review was carried out in PsychInfo and Pubmed database. Considering the absence of peer-reviewed data, review of additional sources of unstructured information from the Internet was carried out between February 2012 and July 2013. Additional searches were conducted using the Global Public Health Intelligence Network (GPHIN), a secure Internet-based early warning system developed by Health Canada and the World Health Organization (WHO), which monitors media reports in six languages, Arabic, Chinese, English, French, Russian, and Spanish. Results: Piracetam is sold via illicit online pharmacies with no need of prescription at low prices. Buyers, mainly healthy individuals, purchase the product to enhance study- and work-related performances as well as for recreational purposes. Its nonmedical use is often associated with the occurrence of side effects such as hallucinations, psychomotor agitation, dysphoria, tiredness, dizziness, memory loss, headache, and severe diarrhoea; moreover, several users declared to have neither felt any cognitive improvement nor psychedelic effects. Conclusions: This is a new and fast-growing trend of abuse that needs to be extensively monitored and studied also by using near real-time and unstructured sources of information such as Internet news and online reports in order to acquire rapid knowledge and understanding. Products sold online might be counterfeits and this enhances related health risksPeer reviewedFinal Accepted Versio

    The Endocannabinoid System: A Putative Role in Neurodegenerative Diseases

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    BACKGROUND: Following the characterization of the chemical structure of D9-tetrahydrocannabinol (THC), the main psychoactive constituent of marijuana, researchers have moved on with scientific valuable explorations. OBJECTIVES: The aim of this review is to highlight the role of endocannabinoid system in neurodegenerative diseases. MATERIALS AND METHODS: The article is a critical analysis of the most recent data currently present in scientific literature on the subject; a qualitative synthesis of only the most significant articles has been performed. RESULTS: In central nervous system, endocannabinoids show a neuromodulatory function, often of retrograde type. This way, they play an important role in synaptic plasticity and in cognitive, motor, sensory and affective processes. In addition, in some acute or chronic pathologies of central nervous system, such as neurodegenerative and neuroinflammatory diseases, endocannabinoids can perform a pro-homeostatic and neuroprotective function, through the activation of CB1 and CB2 receptors. Scientific evidence shows that an hypofunction or a dysregulation of the endocannabinoid system may be responsible for some of the symptoms of diseases such as multiple sclerosis, amyotrophic lateral sclerosis, Huntington’s, Parkinson’s and Alzheimer’s diseases. CONCLUSIONS: The important role played by endocannabinoid system promises interesting developments, in particular to evaluate the effectiveness of new drugs in both psychiatry and neurology

    Alternating block copolymer-based nanoparticles as tools to modulate the loading of multiple chemotherapeutics and imaging probes

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    Abstract Cancer therapy often relies on the combined action of different molecules to overcome drug resistance and enhance patient outcome. Combined strategies relying on molecules with different pharmacokinetics often fail due to the lack of concomitant tumor accumulation and, thus, to the loss of synergistic effect. Due to their ability to enhance treatment efficiency, improve drug pharmacokinetics, and reduce adverse effects, polymer nanoparticles (PNPs) have been widely investigated as co-delivery vehicles for cancer therapies. However, co-encapsulation of different drugs and probes in PNPs requires a flexible polymer platform and a tailored particle design, in which both the bulk and surface properties of the carriers are carefully controlled. In this work, we propose a core-shell PNP design based on a polyurethane (PUR) core and a phospholipid external surface. The modulation of the hydrophilic/hydrophobic balance of the PUR core enhanced the encapsulation of two chemotherapeutics with dramatically different water solubility (Doxorubicin hydrochloride, DOXO and Docetaxel, DCTXL) and of Iron Oxide Nanoparticles for MRI imaging. The outer shell remained unchanged among the platforms, resulting in un-modified cellular uptake and in vivo biodistribution. We demonstrate that the choice of PUR core allowed a high entrapment efficiency of all drugs, superior or comparable to previously reported results, and that higher core hydrophilicity enhances the loading efficiency of the hydrophilic DOXO and the MRI contrast effect. Moreover, we show that changing the PUR core did not alter the surface properties of the carriers, since all particles showed a similar behavior in terms of cell internalization and in vivo biodistribution. We also show that PUR PNPs have high passive tumor accumulation and that they can efficient co-deliver the two drugs to the tumor, reaching an 11-fold higher DOXO/DCTXL ratio in tumor as compared to free drugs. Statement of Significance Exploiting the synergistic action of multiple chemotherapeutics is a promising strategy to improve the outcome of cancer patients, as different agents can simultaneously engage different features of tumor cells and/or their microenvironment. Unfortunately, the choice is limited to drugs with similar pharmacokinetics that can concomitantly accumulate in tumors. To expand the spectrum of agents that can be delivered in combination, we propose a multi-compartmental core-shell nanoparticles approach, in which the core is made of biomaterials with high affinity for drugs of different physical properties. We successfully co-encapsulated Doxorubicin Hydrochloride, Docetaxel, and contrast agents and achieved a significantly higher concomitant accumulation in tumor versus free drugs, demonstrating that nanoparticles can improve synergistic cancer chemotherapy
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