Página 13 dos resultados de 1094 itens digitais encontrados em 0.048 segundos

‣ Epigenetics and T helper 1 differentiation

Aune, Thomas M; Collins, Patrick L; Chang, Shaojing
Fonte: Blackwell Science Inc Publicador: Blackwell Science Inc
Tipo: Artigo de Revista Científica
Publicado em /03/2009 Português
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Naïve T helper cells differentiate into two subsets, T helper 1 and 2, which either transcribe the Ifng gene and silence the Il4 gene or transcribe the Il4 gene and silence the Ifng gene, respectively. This process is an essential feature of the adaptive immune response to a pathogen and the development of long-lasting immunity. The ‘histone code’ hypothesis proposes that formation of stable epigenetic histone marks at a gene locus that activate or repress transcription is essential for cell fate determinations, such as T helper 1/T helper 2 cell fate decisions. Activation and silencing of the Ifng gene are achieved through the creation of stable epigenetic histone marks spanning a region of genomic DNA over 20 times greater than the gene itself. Key transcription factors that drive the T helper 1 lineage decision, signal transducer and activator 4 (STAT4) and T-box expressed in T cells (T-bet), play direct roles in the formation of activating histone marks at the Ifng locus. Conversely, STAT6 and GATA binding protein 3, transcription factors essential for the T helper 2 cell lineage decision, establish repressive histone marks at the Ifng locus. Functional studies demonstrate that multiple genomic elements up to 50 kilobases from Ifng play critical roles in its proper transcriptional regulation. Studies of three-dimensional chromatin conformation indicate that these distal regulatory elements may loop towards Ifng to regulate its transcription. We speculate that these complex mechanisms have evolved to tightly control levels of interferon-γ production...

‣ The Stewart Approach – One Clinician’s Perspective

Morgan, T John
Fonte: The Australian Association of Clinical Biochemists Publicador: The Australian Association of Clinical Biochemists
Tipo: Artigo de Revista Científica
Publicado em /05/2009 Português
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Peter Stewart added controversy to an already troubled subject when he entered the clinical acid-base arena. His approach puts water dissociation at the centre of the acid-base status of body fluids. It is based on six simultaneous equations, incorporating the Laws of Mass Action, Mass Conservation, and Electrical Neutrality. Together with Gibbs-Donnan equilibria, these equations explain the diagnostically important PaCO2/pH relationship, and improve understanding of the physiologic basis of traditional acid-base approaches. Spin-offs have included new scanning tools for unmeasured ions, in particular the ‘strong ion gap’ and ‘net unmeasured ions’. The most controversial feature is the designation of pH and bicarbonate concentrations as dependent variables, answerable exclusively to three independent variables. These are the strong ion difference (SID), the total concentration of non-volatile weak acid (ATOT), and PCO2. Aspects of this assertion conflict with traditional renal physiology, and with current models of membrane H+/base transporters, oxidative phosphorylation, and proton and bicarbonate ionophores. The debate in this area is ongoing. Meanwhile, Stewart-style diagnostic and decision support systems such as the ‘Strong Ion Calculator’ and the web-site www.acidbase.org are now appearing.

‣ Feature-Based Fusion of Medical Imaging Data

Calhoun, Vince D.; Adalı, Tulay
Fonte: PubMed Publicador: PubMed
Tipo: Artigo de Revista Científica
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The acquisition of multiple brain imaging types for a given study is a very common practice. There have been a number of approaches proposed for combining or fusing multitask or multimodal information. These can be roughly divided into those that attempt to study convergence of multimodal imaging, for example, how function and structure are related in the same region of the brain, and those that attempt to study the complementary nature of modalities, for example, utilizing temporal EEG information and spatial functional magnetic resonance imaging information. Within each of these categories, one can attempt data integration (the use of one imaging modality to improve the results of another) or true data fusion (in which multiple modalities are utilized to inform one another). We review both approaches and present a recent computational approach that first preprocesses the data to compute features of interest. The features are then analyzed in a multivariate manner using independent component analysis. We describe the approach in detail and provide examples of how it has been used for different fusion tasks. We also propose a method for selecting which combination of modalities provides the greatest value in discriminating groups. Finally...

‣ The utility of scores in the decision to salvage or amputation in severely injured limbs

Shanmuganathan, Rajasekaran
Fonte: Medknow Publications Publicador: Medknow Publications
Tipo: Artigo de Revista Científica
Publicado em //2008 Português
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The decision to amputate or salvage a severely injured limb can be very challenging to the trauma surgeon. A misjudgment will result in either an unnecessary amputation of a valuable limb or a secondary amputation after failed salvage. Numerous scores have been proposed to provide guidelines to the treating surgeon, the notable of which are Mangled extremity severity score (MESS); the predictive salvage index (PSI); the Limb Salvage Index (LSI); the Nerve Injury, Ischemia, Soft tissue injury, Skeletal injury, Shock and Age of patient (NISSSA) score; and the Hannover fracture scale-97 (HFS-97). These scores have all been designed to evaluate limbs with combined orthopaedic and vascular injuries and have a poor sensitivity and specificity in evaluating IIIB injuries. Recently the Ganga Hospital Score (GHS) has been proposed which is specifically designed to evaluate a IIIB injury. Another notable feature of GHS is that it offers guidelines in the choice of the appropriate reconstruction protocol. The basis of the commonly used scores with their utility have been discussed in this paper.

‣ Where Is the Semantic System? A Critical Review and Meta-Analysis of 120 Functional Neuroimaging Studies

Binder, Jeffrey R.; Desai, Rutvik H.; Graves, William W.; Conant, Lisa L.
Fonte: Oxford University Press Publicador: Oxford University Press
Tipo: Artigo de Revista Científica
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Semantic memory refers to knowledge about people, objects, actions, relations, self, and culture acquired through experience. The neural systems that store and retrieve this information have been studied for many years, but a consensus regarding their identity has not been reached. Using strict inclusion criteria, we analyzed 120 functional neuroimaging studies focusing on semantic processing. Reliable areas of activation in these studies were identified using the activation likelihood estimate (ALE) technique. These activations formed a distinct, left-lateralized network comprised of 7 regions: posterior inferior parietal lobe, middle temporal gyrus, fusiform and parahippocampal gyri, dorsomedial prefrontal cortex, inferior frontal gyrus, ventromedial prefrontal cortex, and posterior cingulate gyrus. Secondary analyses showed specific subregions of this network associated with knowledge of actions, manipulable artifacts, abstract concepts, and concrete concepts. The cortical regions involved in semantic processing can be grouped into 3 broad categories: posterior multimodal and heteromodal association cortex, heteromodal prefrontal cortex, and medial limbic regions. The expansion of these regions in the human relative to the nonhuman primate brain may explain uniquely human capacities to use language productively...

‣ Designing and implementing a skills program Using a clinically integrated, multi-professional approach: Using evaluation to drive curriculum change

Carr, Sandra E.; Celenza, Antonio; Lake, Fiona
Fonte: Medical Education Online Publicador: Medical Education Online
Tipo: Artigo de Revista Científica
Publicado em 20/09/2009 Português
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The essential procedural skills that newly graduated doctors require are rarely defined, do not take into account pre-vocational employer expectations, and differ between Universities. This paper describes how one Faculty used local evaluation data to drive curriculum change and implement a clinically integrated, multi-professional skills program. A curriculum restructure included a review of all undergraduate procedural skills training by academic staff and clinical departments, resulting in a curriculum skills map. Undergraduate training was then linked with postgraduate expectations using the Delphi process to identify the skills requiring structured standardised training. The skills program was designed and implemented without a dedicated simulation center. This paper shows the benefits of an alternate model in which clinical integration of training and multi-professional collaboration encouraged broad ownership of a program and, in turn, impacted the clinical experience obtained.

‣ Update on Recent Advances in the Management of Aspirin Exacerbated Respiratory Disease

Palikhe, Nami Shrestha; Kim, Joo-Hee; Park, Hae-Sim
Fonte: Yonsei University College of Medicine Publicador: Yonsei University College of Medicine
Tipo: Artigo de Revista Científica
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Aspirin intolerant asthma (AIA) is frequently characterized as an aspirin (ASA)-exacerbated respiratory disease (AERD). It is a clinical syndrome associated with chronic severe inflammation in the upper and lower airways resulting in chronic rhinitis, sinusitis, recurrent polyposis, and asthma. AERD generally develops secondary to abnormalities in inflammatory mediators and arachidonic acid biosynthesis expression. Upper and lower airway eosinophil infiltration is a key feature of AERD; however, the exact mechanisms of such chronic eosinophilic inflammation are not fully understood. Cysteinyl leukotriene over-production may be a key factor in the induction of eosinophilic activation. Genetic studies have suggested a role for variability of genes in disease susceptibility and response to medication. Potential genetic biomarkers contributing to the AERD phenotype include HLA-DPB1*301, LTC4S, ALOX5, CYSLT, PGE2, TBXA2R, TBX21, MS4A2, IL10 -1082A > G, ACE -262A > T, and CRTH2 -466T > C; the four-locus SNP set was composed of B2ADR 46A > G, CCR3 -520T > G, CysLTR1 -634C > T, and FCER1B -109T > C. Management of AERD is an important issue. Aspirin ingestion may result in significant morbidity and mortality, and patients must be advised regarding aspirin risk. Leukotriene receptor antagonists (LTRA) that inhibit leukotriene pathways have an established role in long-term AERD management and rhinosinusitis. Aspirin desensitization may be required for the relief of upper and lower airway symptoms in AERD patients. Future research should focus on identification of biomarkers for a comprehensive diagnostic approach.

‣ Of Cattle, Sand Flies and Men: A Systematic Review of Risk Factor Analyses for South Asian Visceral Leishmaniasis and Implications for Elimination

Bern, Caryn; Courtenay, Orin; Alvar, Jorge
Fonte: Public Library of Science Publicador: Public Library of Science
Tipo: Artigo de Revista Científica
Publicado em 09/02/2010 Português
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Visceral leishmaniasis (VL) is a potentially deadly parasitic disease that affects 200,000 to 300,000 people per year in the Indian subcontinent, where an effort is currently underway to eliminate the disease. Studies have identified fairly consistent patterns of risk factors for VL. This information can help to inform the elimination effort. Because humans form the sole source of infection, clustering of VL cases is a prominent feature, both at the household level and on a larger scale. Mud walls, dampness in houses, and peri-domestic vegetation increase infection risk by promoting the survival of the insect vector. Bed nets, sleeping on a cot and indoor residual spraying decrease risk. The presence of cattle is associated with increased risk in some studies and decreased risk in others, reflecting a complex effect on vector abundance and vector infection rates. Poverty is a major underlying factor increasing risk of VL infection and disease. A well-designed demonstration project is needed to provide direct proof of principle for elimination and to identify the most effective maintenance activities to prevent a rapid return of disease when interventions are scaled back.

‣ Tumor-Initiating and -Propagating Cells: Cells That We Would Like to Identify and Control1

Tysnes, Berit Bølge
Fonte: Neoplasia Press Inc. Publicador: Neoplasia Press Inc.
Tipo: Artigo de Revista Científica
Publicado em /07/2010 Português
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Identification of the cell types capable of initiating and sustaining growth of the neoplastic clone in vivo is a fundamental problem in cancer research. It is likely that tumor growth can be sustained both by rare cancer stem-like cells and selected aggressive clones and that the nature of the mutations, the cell of origin, and its environment will contribute to tumor propagation. Genomic instability, suggested as a driving force in tumorigenesis, may be induced by genetic and epigenetic changes. The feature of self-renewal in stem cells is shared with tumor cells, and deviant function of the stem cell regulatory networks may, in complex ways, contribute to malignant transformation and the establishment of a cancer stem cell-like phenotype. Understanding the nature of the more quiescent cancer stem-like cells and their niches has the potential to develop novel cancer therapeutic protocols including pharmacological targeting of self-renewal pathways. Drugs that target cancer-related inflammation may have the potential to reeducate a tumor-promoting microenvironment. Because most epigenetic modifications may be reversible, DNA methylation and histone deacetylase inhibitors can be used to induce reexpression of genes that have been silenced epigenetically. Design of therapies that eliminate cancer stem-like cells without eliminating normal stem cells will be important. Further insight into the mechanisms by which pluripotency transcription factors (e.g....

‣ TLR4 and Insulin Resistance

Kim, Jane J.; Sears, Dorothy D.
Fonte: Hindawi Publishing Corporation Publicador: Hindawi Publishing Corporation
Tipo: Artigo de Revista Científica
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Chronic inflammation is a key feature of insulin resistance and obesity. Toll-Like Receptor 4 (TLR4), involved in modulating innate immunity, is an important mediator of insulin resistance and its comorbidities. TLR4 contributes to the development of insulin resistance and inflammation through its activation by elevated exogenous ligands (e.g., dietary fatty acids and enteric lipopolysaccharide) and endogenous ligands (e.g., free fatty acids) which are elevated in obese states. TLR4, expressed in insulin target tissues, activates proinflammatory kinases JNK, IKK, and p38 that impair insulin signal transduction directly through inhibitory phosphorylation of insulin receptor substrate (IRS) on serine residues. TLR4 activation also leads to increased transcription of pro-inflammatory genes, resulting in elevation of cytokine, chemokine, reactive oxygen species, and eicosanoid levels that promote further insulin-desensitization within the target cell itself and in other cells via paracrine and systemic effects. Increased understanding of cell type-specific TLR4-mediated effects on insulin action present the opportunity and challenge of developing related therapeutic approaches for improving insulin sensitivity while preserving innate immunity.

‣ Molecular insights into amyloid regulation by membrane cholesterol and sphingolipids: common mechanisms in neurodegenerative diseases

Fantini, Jacques; Yahi, Nouara
Fonte: Cambridge University Press Publicador: Cambridge University Press
Tipo: Artigo de Revista Científica
Publicado em /09/2010 Português
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Alzheimer, Parkinson and other neurodegenerative diseases involve a series of brain proteins, referred to as ‘amyloidogenic proteins’, with exceptional conformational plasticity and a high propensity for self-aggregation. Although the mechanisms by which amyloidogenic proteins kill neural cells are not fully understood, a common feature is the concentration of unstructured amyloidogenic monomers on bidimensional membrane lattices. Membrane-bound monomers undergo a series of lipid-dependent conformational changes, leading to the formation of oligomers of varying toxicity rich in β-sheet structures (annular pores, amyloid fibrils) or in α-helix structures (transmembrane channels). Condensed membrane nano- or microdomains formed by sphingolipids and cholesterol are privileged sites for the binding and oligomerisation of amyloidogenic proteins. By controlling the balance between unstructured monomers and α or β conformers (the chaperone effect), sphingolipids can either inhibit or stimulate the oligomerisation of amyloidogenic proteins. Cholesterol has a dual role: regulation of protein–sphingolipid interactions through a fine tuning of sphingolipid conformation (indirect effect)...

‣ The Calcium-Dependent Interaction of S100B with Its Protein Targets

Zimmer, Danna B.; Weber, David J.
Fonte: Hindawi Publishing Corporation Publicador: Hindawi Publishing Corporation
Tipo: Artigo de Revista Científica
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S100B is a calcium signaling protein that is a member of the S100 protein family. An important feature of S100B and most other S100 proteins (S100s) is that they often bind Ca2+ ions relatively weakly in the absence of a protein target; upon binding their target proteins, Ca2+-binding then increases by as much as from 200- to 400-fold. This manuscript reviews the structural basis and physiological significance of increased Ca2+-binding affinity in the presence of protein targets. New information regarding redundancy among family members and the structural domains that mediate the interaction of S100B, and other S100s, with their targets is also presented. It is the diversity among individual S100s, the protein targets that they interact with, and the Ca2+ dependency of these protein-protein interactions that allow S100s to transduce changes in [Ca2+]intracellular levels into spatially and temporally unique biological responses.

‣ T-Cell Dysfunction and Inhibitory Receptors in Hepatitis C Virus Infection

Lee, Jino; Suh, William I.; Shin, Eui-Cheol
Fonte: The Korean Association of Immunologists Publicador: The Korean Association of Immunologists
Tipo: Artigo de Revista Científica
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Dysfunction of the virus-specific T cells is a cardinal feature in chronic persistent viral infections such as one caused by hepatitis C virus (HCV). In chronic HCV infection, virus-specific dysfunctional CD8 T cells often overexpress various inhibitory receptors. Programmed cell death 1 (PD-1) was the first among these inhibitory receptors that were identified to be overexpressed in functionally impaired T cells. The roles of other inhibitory receptors such as cytotoxic T lymphocyte-associated antigen-4 (CTLA-4) and T cell immunoglobulin and mucin domain-containing molecule 3 (Tim-3) have also been demonstrated in T-cell dysfunctions that occur in chronic HCV patients. Blocking these inhibitory receptors in vitro restores the functions of HCV-specific CD8 T cells and allows enhanced proliferation, cytolytic activity and cytokine production. Therefore, the blockade of the inhibitory receptors is considered as a novel strategy for the treatment of chronic HCV infection.

‣ Lipid Mediators in Acne

Ottaviani, Monica; Camera, Emanuela; Picardo, Mauro
Fonte: Hindawi Publishing Corporation Publicador: Hindawi Publishing Corporation
Tipo: Artigo de Revista Científica
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Multiple factors are involved in acne pathogenesis, and sebum secretion is one of the main ones. The role sebum plays in acne development has not been completely elucidated yet; however, increasing amounts of data seem to confirm the presence of alterations in sebum from acne patients. Altered ratio between saturated and unsaturated fatty acids has been indicated as an important feature to be considered in addition to the altered amount of specific fatty acids such as linoleic acid. Furthermore, particular attention has been focused on squalene peroxide that seems to be able to induce an inflammatory response beyond cytotoxicity and comedones formation. Moreover, recent data suggest that lipid mediators are able to interfere with sebocytes differentiation and sebogenesis through the activation of pathways related to peroxisome proliferators-activated receptors. Understanding the factors and mechanisms that regulate sebum production is needed in order to identify novel therapeutic strategies for acne treatment.

‣ Genetics of pulmonary arterial hypertension: do the molecular findings have translational value?

Morrell, Nicholas W
Fonte: Faculty of 1000 Ltd Publicador: Faculty of 1000 Ltd
Tipo: Artigo de Revista Científica
Publicado em 25/03/2010 Português
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Pulmonary arterial hypertension (PAH) is usually a devastating condition with a poor prognosis. Nearly 10 years ago, the underlying molecular basis of heritable PAH was elucidated with the identification of mutations in the gene encoding the bone morphogenetic protein type II receptor (BMPR-II). This discovery is now beginning to suggest novel approaches to therapy in heritable PAH. Moreover, recent studies provide evidence that dysfunction of the BMPR-II pathway is a feature of non-familial forms of PAH, broadening the scope for intervention in this pathway.

‣ Resilience, an Evolving Concept: A Review of Literature Relevant to Aboriginal Research

Fleming, John; Ledogar, Robert J.
Fonte: PubMed Publicador: PubMed
Tipo: Artigo de Revista Científica
Publicado em //2008 Português
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Resilience has been most frequently defined as positive adaptation despite adversity. Over the past 40 years, resilience research has gone through several stages. From an initial focus on the invulnerable or invincible child, psychologists began to recognize that much of what seems to promote resilience originates outside of the individual. This led to a search for resilience factors at the individual, family, community — and, most recently, cultural — levels. In addition to the effects that community and culture have on resilience in individuals, there is growing interest in resilience as a feature of entire communities and cultural groups. Contemporary researchers have found that resilience factors vary in different risk contexts and this has contributed to the notion that resilience is a process. In order to characterize the resilience process in a particular context, it is necessary to identify and measure the risk involved and, in this regard, perceived discrimination and historical trauma are part of the context in many Aboriginal communities. Researchers also seek to understand how particular protective factors interact with risk factors and with other protective factors to support relative resistance. For this purpose they have developed resilience models of three main types: “compensatory...

‣ Lung Cancer Risk and Genetic Polymorphisms in DNA Repair Pathways: A Meta-Analysis

Kiyohara, Chikako; Takayama, Koichi; Nakanishi, Yoichi
Fonte: SAGE-Hindawi Access to Research Publicador: SAGE-Hindawi Access to Research
Tipo: Artigo de Revista Científica
Publicado em 14/10/2010 Português
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Genetic variations in DNA repair genes are thought to modulate DNA repair capacity and are suggested to be related to lung cancer risk. We conducted a meta-analysis of epidemiologic studies on the association between genetic polymorphisms in both base excision repair and nucleotide excision repair pathways, and lung cancer. We found xeroderma pigmentosum complementation group A (XPA) G23A (odds ratio (OR) = 0.76, 95% confidence interval (CI) = 0.61–0.94), 8-oxoguanine DNA glycosylase 1 (OGG1) Ser326Cys (OR = 1.22, 95% CI = 1.02–1.45), and excision repair cross-complementing group 2 (ERCC2) Lys751Gln (OR = 1.27, 95% CI = 1.10–1.46) polymorphisms were associated with lung cancer risk. Considering the data available, it can be conjectured that if there is any risk association between a single SNP and lung cancer, the risk fluctuation will probably be minimal. Advances in the identification of new polymorphisms and in high-throughput genotyping techniques will facilitate the analysis of multiple genes in multiple DNA repair pathways. Therefore, it is likely that the defining feature of future epidemiologic studies will be the simultaneous analysis of large samples of cases and controls.

‣ Vascular Alterations and Sexual Function in Systemic Sclerosis

Impens, Ann Julie; Seibold, James R.
Fonte: Hindawi Publishing Corporation Publicador: Hindawi Publishing Corporation
Tipo: Artigo de Revista Científica
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Sexual dysfunction is common in systemic sclerosis (SSc). Male erectile dysfunction (MED) has been reported in around 80% of subjects and more than half of female patients fulfill criteria for diagnosis as female sexual arousal Disorder (FSAD). While some evidence supports a role for cavernosal fibrosis, abundant data suggest that MED is yet another clinical feature of SSc related to vasculopathy. The contribution of vasculopathy to the more complex issues of female sexual dysfunction is less clear. Inhibitors of Type V phosphodiesterase are effective in men with MED secondary to SSc. Limited study in women suggests inconsistent effects on behavior (frequency) but not on measures related to perfusion. Sexual activity is an important component of quality of life and an important domain for the caregiver to address; it is not clear that it warrants primary consideration as a consistent measure of scleroderma-related vasculopathy.

‣ Relationships between mild traumatic brain injury sustained in combat and post-traumatic stress disorder

Ruff, Robert L; Riechers, Ronald G; Ruff, Suzanne S
Fonte: Medicine Reports Ltd Publicador: Medicine Reports Ltd
Tipo: Artigo de Revista Científica
Publicado em 19/08/2010 Português
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The setting of the trauma is a distinguishing feature between mild traumatic brain injury (mTBI; also called concussion) that occurs in civilian settings compared with that occurring in combat. Combat mTBI is frequently associated with a prolonged stress reaction, post-traumatic stress disorder (PTSD). Individuals with mTBI and PTSD from combat in Operations Iraqi Freedom and Enduring Freedom often develop prolonged post-concussion symptoms (PCSs) such as headache. Both mTBI and PTSD may contribute to PCSs. PTSD may worsen and prolong the PCSs following mTBI by disrupting sleep. It is not known how mTBI predisposes an individual to develop PTSD.

‣ Current Concepts on Antiplatelet Therapy: Focus on the Novel Thienopyridine and Non-Thienopyridine Agents

Testa, L.; Biondi Zoccai, G. G. L.; Valgimigli, M.; Latini, R. A.; Pizzocri, S.; Lanotte, S.; Laudisa, M. L.; Brambilla, N.; Ward, M. R.; Figtree, G. A.; Bedogni, F.; Bhindi, R.
Fonte: Hindawi Publishing Corporation Publicador: Hindawi Publishing Corporation
Tipo: Artigo de Revista Científica
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Thienopyridines are a class of drug targeting the platelet adenosine diphosphate (ADP) 2 receptor. They significantly reduce platelet activity and are therefore clinically beneficial in settings where platelet activation is a key pathophysiological feature, particularly myocardial infarction. Ticlopidine, the first of the class introduced to clinical practice, was soon challenged and almost completely replaced by clopidogrel for its better tolerability. More recently, prasugrel and ticagrelor have been shown to provide a more powerful antiplatelet action compared to clopidogrel but at a cost of higher risk of bleeding complications. Cangrelor, a molecule very similar to ticagrelor, is currently being evaluated against clopidogrel. Considering the key balance of ischemic protection and bleeding risk, this paper discusses the background to the development of prasugrel, ticagrelor, and cangrelor and aims to characterise their risk-benefit profile and possible implementation in daily practice.