Medical hypotheses
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Learning and memory are generally considered the behavioral correlates of long-term potentiation (LTP), a form of synaptic plasticity associated with a persistent and long-lasting increase in synaptic strength. Repetitive stimulation of excitatory synapses in the hippocampal CA1 region leads to release and binding of glutamate to the glutamate receptors AMPAR and NMDAR located on pyramidal neurons. Activation of AMPARs facilitates Na+ influx, postsynaptic depolarization, NMDAR-mediated Ca2+ influx, and activation of several intracellular mechanisms that characterize LTP, including increased AMPAR synthesis, ROS production, and ER Ca2+ release. ⋯ Because both T cell activation and LTP are dependent on intracellular Ca2+ increases and because inhibition of ROS significantly inhibits hippocampal CA1 LTP and T cell activation, it is our hypothesis that AMPK links latent HIV-1 reactivation with hippocampal LTP, learning, and memory. We also propose that compounds that enhance or promote LTP and reactivate latent HIV-1 (e.g. PMA, ionomycin, resveratrol, metformin, etc.) either alone or in combination likely do so via AMPK activation.
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Obstructive jaundice disease is often accompanied by an increase in plasma endogenous opioids levels. Theses elevated endogenous opioids bring complications like pruritus, cardiac and vascular abnormalities in patients with cholestasis. However, little is known about the mechanism of increased endogenous opioids synthesis in cholestatic liver diseases. ⋯ And some cells like keratinocyte and inflammation cells had been proved to correlate with elevated plasma levels of enkephalin and beta-endorphin in patients with obstructive jaundice. Hence, we hypothesize that skin may be the site in which abundant endogenous opioid peptides been produced during the course of obstructive jaundice. These skin-cell related mechanisms should be further studied to resolve the puzzle of elevated peripheral opiate tone during obstructive jaundice.