Cited by 4.1k
Kurchatov Institute
Publishes on Advanced Glycation End Products research, Neuroscience and Neuropharmacology Research, Immune Response and Inflammation. 13 papers and 7.9k citations.
Add your photo, update your bio, and get notified when your ranking changes.
Endotoxin, a constituent of Gram-negative bacteria, stimulates macrophages to release large quantities of tumor necrosis factor (TNF) and interleukin-1 (IL-1), which can precipitate tissue injury and lethal shock (endotoxemia). Antagonists of TNF and IL-1 have shown limited efficacy in clinical trials, possibly because these cytokines are early mediators in pathogenesis. Here a potential late mediator of lethality is identified and characterized in a mouse model. High mobility group-1 (HMG-1) protein was found to be released by cultured macrophages more than 8 hours after stimulation with endotoxin, TNF, or IL-1. Mice showed increased serum levels of HMG-1 from 8 to 32 hours after endotoxin exposure. Delayed administration of antibodies to HMG-1 attenuated endotoxin lethality in mice, and administration of HMG-1 itself was lethal. Septic patients who succumbed to infection had increased serum HMG-1 levels, suggesting that this protein warrants investigation as a therapeutic target.
To study the features of ionic conductance system in termination of sensory units the responses of feline cutaneous A-β mechano-sensitive and C-fiber mechano-heat-sensitive (CMH) units to mechanical and heat stimuli were recorded in intact skin and under the action of subcutaneously applied tetrodotoxin (TTX). Both mechanical and thermal sensitivity of CMH units were not inhibited by 30 μM and in some units by 300 μM TTX, while the responses of A-β units to mechanical stimulation was eliminated by 3 μM TTX. Taking into account the data on low-frequency use-dependent inhibition of CMH unit termination by amine local anesthetics, the availability of TTX-resistant sodium channels in the somatic membrane of C-neurons liable to low-frequency use-dependent inhibition and the slow inactivation of these channels which corresponds to the requirements of mathematical simulation of spike initiation in C-fibers, our results are thought to indicate the presence of TTX-resistant sodium channels in the regenerative region of cutaneous afferent C-fibers.