1,721,481 research outputs found
Per il «Doligamus» di Adolfo di Vienna: le “fabulae” VIII e IX, ovvero alcune variazioni sul tema
Full text linkIl «Doligamus», opera latina in 342 distici elegiaci e 7 esametri leonini degli inizi del sec. XIV (1315), si inserisce pienamente nel filone di poesia misogina di origine clericale che ebbe grande diffusione durante il Medioevo. Il suo autore, Adolfo di Vienna, attinge alla tradizione degli "exempla" e del materiale favolistico per condannare, in nove "fabulae", il comportamento deplorevole delle donne, siano esse mogli infedeli o vecchie diaboliche. In questo lavoro, dopo una presentazione generale dell’autore e dell’opera, ci si sofferma sulle ultime due "fabulae" del «Doligamus», la VIII e la IX, delle quali vengono studiati e analizzati la trama, i modelli, lo stile, la lingua e, soprattutto, le diverse “variazioni sul tema” nell’ambito della produzione novellistica ed esemplare dei secc. XIII e XIV.The «Doligamus», a latin work of 342 elegiac couplets and 7 leonine hexameters of the beginnings of XIVth century (1315), is strictly inserted in the misogynous clerical poetry which had a big diffusion during the Middle Ages. His author, Adolph of Vienna, draws from the tradition of "exempla" and "fabulae" for condemning, in his nine "fabulae", the dreadful manners of women, adulterous wives or diabolic old females. This paper, after a general presentation on the author and the work, offers an analysis of the lost two "fabulae" of the «Doligamus» (fab. VIIIth and IXth), in his plot, sources, style, language and, expecially, in the several “variations on the theme” in the literary production of short stories and "exempla" between XIIIth and XIVth centuries
Alzheimer's Disease and the Routine Clinical Use of CSF Biomarkers
No full textAmyloid based hypothesis led to develop biomarkers oriented diagnosis of neurodegenerative dementias. Among them biomarkers for AD, the most diffuse form of dementia, are currently the unique available for scientific and diagnostic purposes. CSF biomarkers like Amyloid beta 42, total tau and phosphorylated tau levels can be easily evaluated in individuals suffering from cognitive decline, to diagnose or exclude AD type dementia, since early stages. Moreover, their analysis gave the opportunity to better understand cognitive decline patho-physiology during aging. Experience from their use and analysis however showed a high degree of variability due to the great heterogeneity of AD on one hand, the presence of isolated CSF biomarker changes that are not to be considered of AD type and deserve a clinico-pathological classification on the other. Aim of this review is to offer the knowledge about CSF biomarker’s use in clinics
Design of antitumor drugs targeting c-kit receptor by a new mixed ligand-structure based method
Full text linkAn important challenge, in the medicinal chemistry field, is the research of novel forceful drugs to overcome tumor-acquired resistance. The c-Kit tyrosine kinase receptor (TKR) represents a suitable target for the carcinogenesis control of gastro-intestinal stromal (GIST), leukemia, and mastocytosis tumors; nevertheless, several hotspot mutations of the protein limit the efficacy of a few clinical administered TKRs inhibitors. In this study, a new in silico protocol based on ligand and structure-based combined method is proposed, with the aim to identify a set of new c-Kit inhibitors able to complex c-Kit mutated proteins. A recent and freely available web-server DRUDIT is used for the ligand-based method. The protocol application allows for identifying a new generation of potential TKR inhibitors, which, in silico, complex the V654A and T670I mutated proteins and potentially overcome resistant mutations (D816H). The structure-based analysis is performed by Induced Fit Docking (IFD) studies. The comparison between the explored ligands and well-known drugs highlights the possibility to overcome tumor-acquired resistance. The best-selected structures (630705 and SML1348) provide valuable binding affinities with the mutated c-Kit forms (respectively T670I and V654A)
FUCILE DA PESCA SUBACQUEO A DUE FUSTI ORIZZONTALI CON ASTA SINGOLA O DOPPIA
No full textIl brevetto ha per oggetto un fucile subacqueo caratterizzato da due aste, o arpioni, indipendenti che possono essere sparate separatamente. Un’altra variante dell’invenzione prevede una singola asta.
Il brevetto presenta numerosi innovazioni che si traducono in significativi vantaggi funzionali rispetto ai fucili subacquei ad elastico attualmente sul mercato. Oltre ai numerosi benefici derivanti dalla possibilità del doppio sparo, lo schema costruttivo azzera le deformazioni dovute al carico esercitato dagli elastici in tensione di cui soffrono i tradizionali fucili subacquei ad elastico, ne consegue una elevata precisione del tiro anche con fusti di piccolo diametro, molto idrodinamici, realizzati in materiale economico come l’alluminio. La particolare configurazione del fucile consente, anche in presenza della doppia asta, una ubicazione funzionale e quindi una vantaggiosa gestione del filo utilizzato per consentire il recupero del pesce colpito. L’operazione di caricamento dei tradizionali fucili ad elastico non si presenta mai come una operazione facile a causa degli elevatissimi sforzi richiesti alla muscolatura del subacqueo e alla scomoda presa che si ha sugli elastici. Grazie al design del fucile, è possibile realizzare una variante costruttiva opzionale del fucile dove, in alternativa alle tecniche di caricamento tradizionali, sia presente una asta in grado di guidare un componente meccanico avente lo scopo di consentire un agevole caricamento degli elastici. E’ importante sottolineare che l’idrodinamica dell’arma in configurazione a doppia asta è ottimizzata soprattutto rispetto agli spostamenti di brandeggio laterali che sono quelli più frequenti nella normale attività di pesca. Il brandeggio verticale, pur non essendo ottimizzato come nel caso di quello orizzontale, risulterà di pari livello rispetto ad un fucile tradizionale. Il vantaggio della doppia asta coniugato ad una precisione di tiro impareggiabile e ad un basso costo costruttivo potrebbe consentire al fucile di affermarsi con successo sul mercato nazionale e internazionale. La variante ad asta singola, pur non avvantaggiandosi della possibilità del doppio colpo, mantiene una precisione di tiro impareggiabile in relazione al costo costruttivo molto basso
Old facts and new perspectives to face Alzheimer?s dementia. Focus on non neuronal participants to neurodegeneration
No full text
Transcranial magnetic stimulation: emerging biomarkers and novel therapeutics in Alzheimer's disease
No full textAlzheimer's disease (AD) is one of the most devastating conditions affecting
elderly in Western World. Unfortunately, there are no effective treatments, and
patients diagnosed with AD face an uncertain future, caused by the current
inability to predict the course of the disease. This is mainly due to the poor
comprehension of AD pathophysiology and of patients' clinical heterogeneity. In
recent years, several evidences supported the concept that loss of synaptic
density could be an early event and precede neuronal degeneration, suggesting
that the impairment of synaptic transmission should play a key role in the
pathogenesis of different forms of dementia, including AD, frontotemporal
dementia and Lewy body dementia. Despite this emerging background it has not been
possible to quantify synaptic functioning (or dysfunction) directly in vivo in AD
patients. Transcranial magnetic stimulation (TMS) has been recently introduced as
a novel approach able to identify the early signatures of synaptic dysfunction
characterizing the different forms of AD. We review the novel emerging
neurophysiological signatures of AD and how this information may be used as
biomarkers for differential diagnosis, disease progression and response to
therapy. Finally, we also consider novel therapeutic approaches based on the
clinical use of repetitive TMS
Beyond the cholinergic hypothesis: Do current drugs work in alzheimer's disease?
No full textAlzheimer’s disease (AD) is a neurodegenerative disease characterized bymemory and cognitive loss, and represents the leading cause of dementia inelderly people. Besides the complex biochemical processes involved in the neu-ronal degeneration (formation of senile plaques containing Aβ peptides, anddevelopment of neurofibrillary tangles), other molecular and neurochemicalalterations, like cholinergic deficit due to basal forebrain degeneration, alsooccur. Because acetylcholine has been demonstrated to be involved in cog-nitive processes, the idea to increase acetylcholine levels to restore cognitivedeficits has gained interest (the so-called cholinergic hypothesis). This has ledto the development of drugs able to prevent acetylcholine hydrolysis (acetyl-cholinesterase inhibitors). However, the analysis of clinical efficacy of thesedrugs in alleviating symptoms of dementia showed unsatisfactory results. De-spite such critical opinions on the efficacy of these drugs, it should be said thatacetylcholinesterase inhibitors, and for some aspects memantine also, improvememory and other cognitive functions throughout most of the duration of thedisease. The pharmacological activity of these drugs suggests an effect beyondthe mere increase of acetylcholine levels. These considerations are in agree-ment with the idea that cognitive decline is the result of a complex and notfully elucidated interplay among different neurotransmitters. The role of eachof the neurotransmitters implicated has to be related to a cognitive process andas a consequence to its decline. The current review aims to highlight the pos-itive role of cholinergic drugs in alleviating cognitive deficits during wake aswell as sleep. Moreover, we suggest that future therapeutic approaches haveto be developed to restore the complex interplay between acetylcholine andother neurotransmitters systems, such as dopamine, serotonin, noradrenaline,or glutamate, that are likely involved in the progressive deterioration of severalcognitive functions such as attention, memory, and learning.Alzheimer's disease (AD) is a neurodegenerative disease characterized by memory and cognitive loss, and represents the leading cause of dementia in elderly people. Besides the complex biochemical processes involved in the neuronal degeneration (formation of senile plaques containing Aβ peptides, and development of neurofibrillary tangles), other molecular and neurochemical alterations, like cholinergic deficit due to basal forebrain degeneration, also occur. Because acetylcholine has been demonstrated to be involved in cognitive processes, the idea to increase acetylcholine levels to restore cognitive deficits has gained interest (the so-called cholinergic hypothesis). This has led to the development of drugs able to prevent acetylcholine hydrolysis (acetylcholinesterase inhibitors). However, the analysis of clinical efficacy of these drugs in alleviating symptoms of dementia showed unsatisfactory results. Despite such critical opinions on the efficacy of these drugs, it should be said that acetylcholinesterase inhibitors, and for some aspects memantine also, improve memory and other cognitive functions throughout most of the duration of the disease. The pharmacological activity of these drugs suggests an effect beyond the mere increase of acetylcholine levels. These considerations are in agreement with the idea that cognitive decline is the result of a complex and not fully elucidated interplay among different neurotransmitters. The role of each of the neurotransmitters implicated has to be related to a cognitive process and as a consequence to its decline. The current review aims to highlight the positive role of cholinergic drugs in alleviating cognitive deficits during wake as well as sleep. Moreover, we suggest that future therapeutic approaches have to be developed to restore the complex interplay between acetylcholine and other neurotransmitters systems, such as dopamine, serotonin, noradrenaline, or glutamate, that are likely involved in the progressive deterioration of several cognitive functions such as attention, memory, and learning. © 2010 Blackwell Publishing Ltd
Quinoline-based molecules targeting c-Met, EGF, and VEGF receptors and the proteins involved in related carcinogenic pathways
Full text linkThe quinoline ring system has long been known as a versatile nucleus in the design and synthesis of biologically active compounds. Currently, more than one hundred quinoline compounds have been approved in therapy as antimicrobial, local anaesthetic, antipsychotic, and anticancer drugs. In drug discovery, indeed, over the last few years, an increase in the publication of papers and patents about quinoline derivatives possessing antiproliferative properties has been observed. This trend can be justified by the versatility and accessibility of the quinoline scaffold, from which new derivatives can be easily designed and synthesized. Within the numerous quinoline small molecules developed as antiproliferative drugs, this review is focused on compounds effective on c-Met, VEGF (vascular endothelial growth factor), and EGF (epidermal growth factor) receptors, pivotal targets for the activation of important carcinogenic pathways (Ras/Raf/MEK and PI3K/AkT/mTOR). These signalling cascades are closely connected and regulate the survival processes in the cell, such as proliferation, apoptosis, differentiation, and angiogenesis. The antiproliferative biological data of remarkable quinoline compounds have been analysed, confirming the pivotal importance of this ring system in the efficacy of several approved drugs. Furthermore, in view of an SAR (structure-activity relationship) study, the most recurrent ligand–protein interactions of the reviewed molecules are summarized
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