Voltage-Gated Sodium Channel Pharmacology: Insights From Molecular Dynamics Simulations.
Voltage-Gated Sodium Channel Pharmacology: Insights From Molecular Dynamics Simulations. Adv Pharmacol. 2017;79:255-285 Authors: Chen R, Buyan A, Corry B Abstract Voltage-gated ion channels are the target of a range of naturally occurring toxins and therapeutic drugs. There is a great interest in better understanding how these diverse compounds alter channel function in order to design the next generation of therapeutics that can selectively target one of the channel subtypes found in the body. Since the publication of a number of bacterial sodium channel structures, molecular dynamics simulations have been invaluable in gaining a high resolution understanding where many of these small molecules and toxins bind to the channels, how they find their binding site, and how they can selectively bind to one channel subtype over another. This chapter summarizes these recent studies to highlight what has been learnt about channel pharmacology using computer simulations and to draw out shared conclusions, focusing separately on toxin-channel interactions and small molecule-channel interactions. PMID: 28528671 [PubMed - in process]
In conclusion, BLU-5937 was selected as a drug candidate for the treatment of chronic cough due to its high potency and selectivity for P2X3 homotrimeric receptors, strong anti-tussive effects, excellent tolerability and predicted pharmacokinetic properties in humans.
ConclusionThe SOS presents nearly as good as the SOFA score, to predict mortality among sepsis patients admitted to the ICU. The early warning score is another, alternative tool to use for risk stratification and sepsis screening for ICU sepsis patients.
Conclusions: Echogenicity of a pleural effusion has a low specificity for identifying an underlying exudate, and the echogenic qualities of the fluid should not influence clinical decision-making.Respiration
MRC Laboratory of Molecular Biology researchers reveal atomic structures of the abnormal tau filaments associated with chronic traumatic encephalopathy, a head injury-associated neurodegenerative disease, differ in structure from those seen in Alzheimer’s disease.
ConclusionsThese findings indicate that the neural effects of AUD vary according to severity. Our results emphasize the utility of resting state fMRI as a neuroimaging biomarker for quantitative clinical evaluation of AUD.
Publication date: Available online 19 March 2019Source: NeuroImage: ClinicalAuthor(s): Jason A. Martin, Nadine Zimmermann, Lukas Scheef, Jakob Jankowski, Sebastian Paus, Hans H. Schild, Thomas Klockgether, Henning BoeckerAbstractMany studies have used functional magnetic resonance imaging to unravel the neuronal underpinnings of motor system abnormalities in Parkinson's disease, indicating functional inhibition at the level of basal ganglia-thalamo-cortical motor networks. The study aim was to extend the characterization of functional motor changes in Parkinson's Disease by dissociating between two phases of action (i.e. m...
ConclusionsA clinically relevant model of PTA of venous stenosis in mice was created. PTA-treated vessels had increased lumen vessel area and WSS. The alterations in tissue markers of vascular remodeling, tissue hypoxia, proliferation, and cell death may be implications for future design of drug and device development.
ConclusionWEB shape modification was observed in more than half of cases but with no influence regarding adequate occlusion rate. This quantitative approach of WSM highlights that this phenomenon appears to be early and progressive over time. This supports the hypothesis that WSM could be more probably related to aneurysm healing rather than external compression.
AI limitations, no-show cures, and more in this month's radiology comics.