Articles: function.
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Anesthesia and analgesia · Apr 2015
Tramadol and Its Metabolite M1 Selectively Suppress Transient Receptor Potential Ankyrin 1 Activity, but Not Transient Receptor Potential Vanilloid 1 Activity.
The transient receptor potential vanilloid 1 (TRPV1) and the transient receptor potential ankyrin 1 (TRPA1), which are expressed in sensory neurons, are polymodal nonselective cation channels that sense noxious stimuli. Recent reports showed that these channels play important roles in inflammatory, neuropathic, or cancer pain, suggesting that they may serve as attractive analgesic pharmacological targets. Tramadol is an effective analgesic that is widely used in clinical practice. Reportedly, tramadol and its metabolite (M1) bind to μ-opioid receptors and/or inhibit reuptake of monoamines in the central nervous system, resulting in the activation of the descending inhibitory system. However, the fundamental mechanisms of tramadol in pain control remain unclear. TRPV1 and TRPA1 may be targets of tramadol; however, they have not been studied extensively. ⋯ These data indicate that tramadol and M1 selectively inhibit the function of hTRPA1, but not that of hTRPV1, and that hTRPA1 may play a role in the analgesic effects of these compounds.
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Journal of anesthesia · Apr 2015
ReviewImplications of recent accumulating knowledge about endothelial glycocalyx on anesthetic management.
The endothelial glycocalyx is a labile, fine structure coating the luminal membrane of intact healthy vascular endothelium. For many decades, no physiologic importance was linked to this structure. It is crucial for vascular barrier function. ⋯ Perioperative damage of the glycocalyx has been demonstrated, and is linked with morbidity and even mortality in surgical patients. Research on the glycocalyx should change many of the current perioperative management guidelines, and focusing on its protection is plausible. The present article reviews what we already know about the glycocalyx and how this knowledge has changed anesthesiologist perspectives.
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Semin Respir Crit Care Med · Apr 2015
ReviewCystic fibrosis transmembrane conductance regulator modulators: the end of the beginning.
Cystic fibrosis (CF) represents one of the success stories of modern medicine with sustained incremental increases in the survival from one of childhood death to one of adult survival into the middle decades over the past 30 years. Improving survival has focused on multidisciplinary management centered on treating the consequences of this genetic disease. It has been firmly established for more than 20 years that mutations in the CF transmembrane conductance regulator (CFTR) gene result in a defective protein that normally functions as a chloride channel on epithelial cell surfaces. ⋯ This review highlights the evidence to date on efforts to modulate CFTR and restore robust functional protein to the cell surface. This approach has now led to the licensing of one CFTR potentiator, which has been shown to have significant clinical improvements in a subset of CF patients. This success represents the beginning for CFTR modulation and further research is ongoing which aims to broaden the applicability of these techniques.
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A role of the serotonin (5HT) transporter, a key regulator of serotonergic transmission, in the physiology, pharmacology and genetics of pain responses has been proposed recently. The present study aimed to explore the impact of constitutive differences in the activity of the serotonin transporter, and 5HT homeostasis in general, on the modulation on pain sensitivity and analgesic responses to drugs that utilize 5HT mechanisms. ⋯ These findings support the idea that functionality of the serotonin transporter is one of the physiological/genetic determinants of individual differences in pain responses and modulation. They also validate Wistar-Zagreb 5HT rats, with constitutionally up-regulated/down-regulated serotonin transporter, as a potential new genetic model for studying serotonergic modulation of pain responses.
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The aim of this study was to determine the ability of the central sensitization inventory (CSI), a new screening instrument, to assist clinicians in identifying patients with central sensitivity syndromes (CSSs). ⋯ The CSI is a useful and valid instrument for screening patients for the possibility of a CSS, although the chances of false positives are relatively high when evaluating patients with complex pain and psychophysiological disorders.