Current pharmaceutical design
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Low-density lipoprotein receptor related protein-1 (LRP) is a member of the low-density lipoprotein (LDL) receptor family which has been linked to Alzheimer's disease (AD) by biochemical and genetic evidence. Levels of neurotoxic amyloid beta-peptide (Abeta) in the brain are elevated in AD contributing to the disease process and neuropathology. Faulty Abeta clearance from the brain appears to mediate focal Abeta accumulations in AD. ⋯ In AD individuals, the levels of LRP at the BBB are reduced, as are levels of Abeta binding to sLRP in plasma. This, in turn, may increase Abeta brain levels through a decreased efflux of brain Abeta at the BBB and/or reduced sequestration of plasma Abeta associated with re-entry of free Abeta into the brain via RAGE. Thus, therapies which increase LRP expression at the BBB and/or enhance the peripheral Abeta "sink" activity of sLRP, hold potential to control brain Abeta accumulations, neuroinflammation and cerebral blood flow reductions in AD.
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Advanced glycation end products (AGEs) are a heterogeneous group of molecules, formed in vivo both by non-oxidative and oxidative reactions of sugars and their adducts to proteins and lipids. It is now well established that formation and accumulation of AGEs progress during normal aging, and at an extremely accelerated rate under diabetes, thus being implicated in various types of AGEs-related disorders such as diabetic vascular complications, neurodegenerative diseases and cancers. There is a growing body of evidence that activation of RAGE (receptor for AGEs) system is also implicated in these devastating disorders. ⋯ Liver is not only a target organ, but also an important site for clearance and catabolism of circulating AGEs. Although there are several papers to suggest the involvement of AGEs-RAGE system in various types of liver diseases such as non-alcoholic steatohepatitis, liver cirrhosis and cancers, as far as we know, there are few comprehensive reviews to deal with this issue. Therefore, in this paper, we shortly review the pathological role of AGEs and RAGE in various liver diseases.
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Review
Characterization of supraventricular tachycardia in infants: clinical and instrumental diagnosis.
Supraventricular tachycardia (SVT) is the most common symptomatic arrhythmias in children. Re-entry tachycardias are the most common form, on the contrary automatic tachycardias are relatively rare. There are four types or re-entry: along anomalous pathway with bi-directional (Wolff-Parkinson-White) or unidirectional conduction, intranodal re-entry, intra-atrial re-entry that is common after surgical procedure, and finally the uncommon sinus node re-entry. ⋯ Patients with SVT require a complete evaluation with others diagnostic techniques: echocardiogram, Holter monitoring, stress test, that should be chosen according the type of tachycardia. Electrophysiologic evaluation is now rarely performed for diagnostic purpose; trans-esophageal atrial stimulation being less invasive than intracardiac evaluation is more extensively employed when diagnosis of SVT is uncertain. Transesophageal stimulation is useful in the following situations: 1) evaluation of patients with symptoms suggestive of paroxistic tachycardia but without ecg documentation, 2) to assess the mechanism responsible for re-entry tachycardia: macro re-entry versus intranodal re-entry 3) to evaluate characteristics of anomalous pathway with bi-directional conduction, and 4)to terminate re-entrant SVT.
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The host's inflammatory response to sepsis can be divided into two phases, the initial detection and response to the pathogen initiated by the innate immune response, and the persistent inflammatory state characterized by multiple organ dysfunction syndrome (MODS). New therapies aimed at pathogen recognition receptors (PRRs) particularly the TLRs and the NOD-like receptors offer hope to suppress the initial inflammatory response in early sepsis and to bolster this response in late sepsis. The persistence of MODS after the initial inflammatory surge can also be a determining factor to host survival. ⋯ In addition. severe loss of mitochondria results in low cell energy stores, necrotic cell death, and increased inflammation driven by the release of cell components such as HMGB1. Therapies, which aim at improving cellular energy reserves such as the promotion of mitochondrial biogenesis by insulin, may have a role in future sepsis therapies. Finally, both the inflammatory responses and the susceptibility to organ failure may be modulated by nutritional status and micronutrients, such as zinc, Therapies aimed at micronutrient repletion may further augment approaches targeting PRR function and mitochondrial viability.
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Neuromuscular blocking agents are the leading drugs responsible for immediate hypersensitivity reactions during anaesthesia. Most hypersensitivity reactions represent IgE-mediated allergic reactions. Their incidence is estimated to be between 1 in 3,000 to 1 in 110,000 general anaesthetics. ⋯ There is no demonstrated evidence supporting systematic pre-operative screening in the general population at this time. However, since no specific treatment has been shown to reliably prevent anaphylaxis, allergy assessment must be performed in all high-risk patients. In view of the relative complexity of allergy investigation, and of the differences between countries, an active policy to identify patients at risk and to provide any necessary support from expert advice to anaesthetists and allergologists through the constitution of allergo-anaesthesia centres in every country should be promoted.