1,721,036 research outputs found
Therapeutic potential of A2 and A3 adenosine receptor: a review of novel patented ligands.
No full textIntroduction: Adenosine exerts its effects by interacting with G-protein coupled receptors (GPCR) namely A1, A2A, A2B and A3, respectively. These are involved in several diseases, for example and most importantly, Parkinson’s disease, ischemia and inflammation. There is high interest in the development of potent and selective ligands for these adenosine receptor (AR) subtypes, primarily for their therapeutic potential but also as pharmacological tools in receptor studies.
Areas covered: This paper concentrates on reviewing the therapeutic potential of A2 and A3 ARs, which represent the most interesting subtypes of recent years. A general description of each receptor is reported with novel agonist and antagonist structures, patented in 2008 -- 2011. PubMed and Free Patents Online databases were principally used to collect all the material.
Expert opinion: In the past years, by modulating A2 and A3ARs, several new possible therapeutic applications were discovered. For this reason, research concerning AR ligands is still of great interest. In particular, few potent and selective A2B agonists and antagonists are actually reported and a clear SAR (structure--activity relationship) profile lacks for this AR subtype. At the A3AR, allosteric modulation may prevent problems related to the high difference between rat and human orthosteric sites and simplify the preclinical studies on A3AR
Chimica farmaceutica. Capitolo 24. Farmaci antiulcera
No full textAttraverso uno stile leggibile e accattivante, il testo offre una comprensione esaustiva delle fasi di progettazione dei farmaci e dei meccanismi molecolari attraverso cui un farmaco esercita la sua azione all'interno di un organismo. Il libro rappresenta un'opera con l'ambizione di diventare un punto di riferimento nell'insegnamento della Chimica farmaceutica in Italia. Il testo sottolinea l'importanza della Chimica farmaceutica nelle nostre vite, evidenziando il fascino di una disciplina che integra chimica, biochimica, fisiologia, microbiologia, biologia cellulare e farmacologia. Sarà quindi di grande interesse per tutti quegli studenti che aspirano a una carriera futura nell'industria farmaceutica
Promising Targets and Strategies to Control Neuroinflammation (Part I)
Full text linkNeuroinflammation is a condition in which inflammation occurs in the central nervous system (CNS: brain and
spinal cord), leading to the activation of microglia and astrocytes. Its role in several central pathologies is nowadays
well-known, including neurodegenerative diseases like Alzheimer's disease (AD), Parkinson's disease (PD), multiple
sclerosis (MS) and amyotrophic lateral sclerosis (ALS) [1]. In fact, neuroinflammation has the role of restoring
homeostasis in the CNS when an injury occurs. On the contrary, sustained inflammation is detrimental, and this typically
occurs in and characterizes neurodegenerative diseases. The formation of protein aggregates distinctive to
neurodegenerative diseases is one of the stimuli that exacerbate neuroinflammation [2]. Thus, searching for targets
involved in the control of the neuroinflammatory condition in these still incurable diseases continuously attracts the
scientific community's attention. In particular, several enzymes and receptors have been investigated for their role in
neuroinflammation and neurodegeneration. In this thematic issue, promising targets and their ligands are discussed
with strategies to develop entities able to control neuroinflammation.
In particular, in this first part of the thematic issue, the discussed targets by eminent research groups are protein kinases.
The first contribution, "Glycogen Synthase Kinase 3β Involvement in Neuroinflammation and Neurodegenerative
Diseases” by Gianferrara et al., describes GSK3β structure and its involvement in both neuroinflammation and neurodegeneration
as well as GSK3β inhibitors with a special focus on that used in preclinical or clinical studies [3].
The second contribution, titled “Casein Kinase 1δ Inhibitors as Promising Therapeutic Agents for Neurodegenerative
Disorders,” by Catarzi et al., highlights the development of CK1δ inhibitors, on their structure-activity relationships
comprising computational studies which provide useful insight for the design of novel inhibitors [4].
The third contribution, titled “Role of Fyn Kinase Inhibitors in Switching Neuroinflammatory Pathways” by Marotta
et al., reviews efforts to develop small molecules that inhibit Fyn, as an opportunity for therapeutic intervention
in neurodegeneration [5].
The fourth and last contribution, titled “Computational Strategies to Identify New Drug Candidates against Neuroinflammation”
by Pavan et al., aims to provide a general overview of the most common computational strategies that can
be exploited to discover and design small molecules controlling neuroinflammation, reporting several case studies [6].
We are grateful to all the eminent authors for their valuable contributions that have allowed us to make this thematic
issue. We also thank the Italian Ministry of University and Research (MUR) for the financial support within
the PRIN2017 (Grant no. 2017MT3993)
Promising Targets and Strategies to Control Neuroinflammation (Part II)
Full text linkNeuroinflammation is the condition in which inflammation occurs in the central nervous system (CNS: brain and
spinal cord), leading to the activation of microglia and astrocytes. Its role in several central pathologies is nowadays
well-known, including neurodegenerative diseases like Alzheimer's disease (AD), Parkinson's disease (PD), multiple
sclerosis (MS) and amyotrophic lateral sclerosis (ALS) [1]. In fact, neuroinflammation has the role of restoring
homeostasis in the CNS when an injury occurs. On the contrary, sustained inflammation is detrimental, and this typically
occurs in and characterizes neurodegenerative diseases. The formation of protein aggregates distinctive to
neurodegenerative diseases is one of the stimuli that exacerbate neuroinflammation [2]. Thus, searching for targets
involved in the control of the neuroinflammatory condition in these still incurable diseases continuously attracts the
scientific community's attention. In particular, several enzymes and receptors have been investigated for their role in
neuroinflammation and neurodegeneration. In this thematic issue, promising targets and their ligands are discussed
with strategies to develop entities able to control neuroinflammation.
In particular, in this second part of the thematic issue, the discussed targets by eminent research groups are G
protein-coupled receptors and the mitochondrial translocator protein TSPO. The first contribution, "A2A Adenosine
Receptor Antagonists and their Potential in Neurological Disorders” by Lambertucci et al., highlights the neuroprotective
effects mediated by the A2A adenosine receptor antagonists summarizing most relevant and promising compounds
along with their preclinical and clinical studies in neuroinflammation related diseases [3].
The second contribution, titled “Interplay Between Endocannabinoid System and Neurodegeneration: Focus on
Polypharmacology,” by Seghetti et al. is focused on the most recent studies evaluating the role of cannabinoids in
neurodegenerative diseases, especially on the potential for a multitarget strategy [4].
The third contribution, titled “Translocator Protein 18-kDa: A Promising Target to Treat Neuroinflammationrelated
Degenerative Diseases,” by Tremolanti et al. reviews recent findings on the potential immunomodulatory
effects of TSPO ligands against neuroinflammation, taking into consideration some pathologies of the nervous system
in which inflammatory events are crucial for the onset and progression of the disease [5]. The last contribution,
titled “Essential Principles and Recent Progress in the Development of TSPO PET Ligands for Neuroinflammation
Imaging,” by Viviano et al. focuses on TSPO. This review discussed the design and development of TSPO PET
ligands useful for assessing active gliosis associated with brain lesions following injury or disease [6].
We are grateful to all the eminent authors for their valuable contributions that have allowed us to make this thematic
issue. We also thank the Italian Ministry of University and Research (MUR) for the financial support within
the PRIN2017 (Grant no. 2017MT3993)
Anticonvulsivanti
No full textL’epilessia è una sindrome neurologica caratterizzata da crisi epilettiche ricorrenti e imprevedibili. Nel mondo ne sono colpite 50 milioni di persone, l’80% delle quali proviene da paesi in via di sviluppo. Il termine crisi epilettica indica un’alterazione transitoria dell’attività cerebrale causata da scariche neuronali anomale, eccessive e sincrone, che colpiscono intere popolazioni di neuroni. Queste scariche possono causare piccoli movimenti involontari, forti convulsioni, alterazioni psichiche, perdita dell’attenzione e addirittura alterare lo stato di coscienza. Una crisi può essere definita non epilettica quando provocata in un cervello normale tramite elettroshock o sostanze convulsivanti. Le diverse tipologie di crisi epilettiche possono essere classificate, secondo i sintomi clinici e il tracciato EEG (elettroencefalogramma), in crisi parziali e generalizzate. Le crisi parziali originano da un punto preciso (focale) di uno degli emisferi cerebrali, mentre le crisi generalizzate coinvolgono l’intero cervello e non è possibile localizzare un’origine precisa dell’impulso. Benché si possano distinguere epilessie di tipo idiopatico ed epilessie di tipo sintomatico (causate da lesioni come trauma o infarto cerebrale), l’eziologia di tali sindromi rimane ignota. Per tale motivo i farmaci attualmente a disposizione sono anticonvulsivanti, cioè contrastano il sintomo, la crisi epilettica (le convulsioni), ma non prevengono o curano l’epilessia. I farmaci anticonvulsivanti in uso riescono a controllare le crisi nel 70-80% dei pazienti, mentre falliscono nel restante 20-30% dei casi
Going Beyond Counting First Authors in Author Co-citation Analysis
Full text linkThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
Variations on the Author
Full text link“Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship
Appropriate Similarity Measures for Author Cocitation Analysis
Full text linkWe provide a number of new insights into the methodological discussion about author cocitation analysis. We first argue that the use of the Pearson correlation for measuring the similarity between authors’ cocitation profiles is not very satisfactory. We then discuss what kind of similarity measures may be used as an alternative to the Pearson correlation. We consider three similarity measures in particular. One is the well-known cosine. The other two similarity measures have not been used before in the bibliometric literature. Finally, we show by means of an example that our findings have a high practical relevance.information science;Pearson correlation;cosine;similarity measure;author cocitation analysis
Receptor Driven Identifications of Novel Human A3 adenosine receptor antagonists as Potential therapeutic agents.
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