Results from clinical trials show that serotonergic psychedelics have efficacy in treating psychiatric disorders, where currently approved pharmacotherapies are inadequate. Developing psychedelic medicines, however, comes with unique challenges, such as tempering heightened anxiety associated with the psychedelic experience. We conceived a new strategy to potentially mitigate psychedelic effects with defined electromagnetic signals (ES).
View Article and Find Full Text PDFBackground: Astrocytes Ca signaling play a central role in the modulation of neuronal function. Activation of metabotropic glutamate receptors (mGluR) by glutamate released during an increase in synaptic activity triggers coordinated Ca signals in astrocytes. Importantly, astrocytes express the Ca-dependent nitric oxide (NO)-synthetizing enzymes eNOS and nNOS, which might contribute to the Ca signals by triggering Ca influx or ATP release through the activation of connexin 43 (Cx43) hemichannels, pannexin-1 (Panx-1) channels or Ca homeostasis modulator 1 (CALHM1) channels.
View Article and Find Full Text PDFEndothelial cell migration is a key process in angiogenesis. Progress of endothelial cell migration is orchestrated by coordinated generation of Ca signals through a mechanism organized in caveolar microdomains. Connexins (Cx) play a central role in coordination of endothelial cell function, directly by cell-to-cell communication via gap junction and, indirectly, by the release of autocrine/paracrine signals through Cx-formed hemichannels.
View Article and Find Full Text PDFVascular system is a complex network in which different cell types and vascular segments must work in concert to regulate blood flow distribution and arterial blood pressure. Although paracrine/autocrine signaling is involved in the regulation of vasomotor tone, direct intercellular communication via gap junctions plays a central role in the control and coordination of vascular function in the microvascular network. Gap junctions are made up by connexin (Cx) proteins, and among the four Cxs expressed in the cardiovascular system (Cx37, Cx40, Cx43, and Cx45), Cx40 has emerged as a critical signaling pathway in the vessel wall.
View Article and Find Full Text PDFEMulate Therapeutics, Inc. (EMTx) has developed a technology to deliver time-varying magnetic fields as WAV files, emitted in the extremely low through the low spectrum of radio frequencies (DC to 22 kHz), that can be applied to regulate pain sensation. These low power fields (~30-70 milli-Gauss AC RMS) are delivered via a portable, light-weight wearable device (Voyager).
View Article and Find Full Text PDFBackground: SARs-Cov-2 infections can produce prolonged illness and significant disability. Patients recovering from COVID-19 can have persistent symptoms leading to long-term morbidity.
Methods: Six patients with long-lasting (> 30 days) COVID-19 symptoms were treated with hyperbaric oxygen (HBO2) therapy.
The goal of the present study was to estimate the radiation dose for a group of 45 Kawasaki disease (KD) patients undergoing fluoroscopically guided cardiac catheterization. The sample of procedures corresponds to a single hospital and was collected in 10 years. Anthropometric characteristics and the quantities of air kerma-area product (PKA) among others were recorded for each procedure.
View Article and Find Full Text PDFDeletion of pannexin-1 (Panx-1) leads not only to a reduction in endothelium-derived hyperpolarization but also to an increase in NO-mediated vasodilation. Therefore, we evaluated the participation of Panx-1-formed channels in the control of membrane potential and [Ca] of endothelial cells. Changes in NO-mediated vasodilation, membrane potential, superoxide anion (O ) formation, and endothelial cell [Ca] were analyzed in rat isolated mesenteric arterial beds and primary cultures of mesenteric endothelial cells.
View Article and Find Full Text PDFInteracting receptors at the neuronal plasma membrane represent an additional regulatory mode for intracellular transduction pathways. P2X4 receptor triggers fast neurotransmission responses a transient increase in intracellular Ca levels. It has been proposed that the P2X4 receptor interacts with the 5-HTA receptor in hippocampal neurons, but their binding stoichiometry and the role of P2X4 receptor activation by ATP on this crosstalking system remains unknown.
View Article and Find Full Text PDFBlood flow distribution relies on precise coordinated control of vasomotor tone of resistance arteries by complex signalling interactions between perivascular nerves and endothelial cells. Sympathetic nerves are vasoconstrictors, whereas endothelium-dependent NO production provides a vasodilator component. In addition, resistance vessels are also innervated by sensory nerves, which are activated during inflammation and cause vasodilation by the release of calcitonin gene-related peptide (CGRP).
View Article and Find Full Text PDFThe aims of the present study were to present the frequency of multiple interventional cardiac procedures for a certain group of patients obtained at one of the largest paediatric hospitals in Chile. In addition it has been analysed cumulative kerma area product (KAP) and cumulative air kerma (CAK), and calculated organ doses for the patient groups undergoing 2, 3 and ≥ 4 procedures, using Monte Carlo software. Effective doses were also estimated for epidemiological purposes and to permit comparison with other imaging procedures.
View Article and Find Full Text PDFConnexins (Cxs) and pannexins (Panxs) are ubiquitous membrane channel forming proteins that are critically involved in many aspects of vascular physiology and pathology. The permeation of ions and small metabolites through Panx channels, Cx hemichannels and gap junction channels confers a crucial role to these proteins in intercellular communication and in maintaining tissue homeostasis. This review provides an overview of current knowledge with respect to the pathophysiological role of these channels in large arteries, the microcirculation, veins, the lymphatic system and platelet function.
View Article and Find Full Text PDFNa-Ca exchanger (NCX) contributes to control the intracellular free Ca concentration ([Ca]), but the functional activation of NCX reverse mode (NCXrm) in endothelial cells is controversial. We evaluated the participation of NCXrm-mediated Ca uptake in the endothelium-dependent vasodilation of rat isolated mesenteric arterial beds. In phenylephrine-contracted mesenteries, the acetylcholine (ACh)-induced vasodilation was abolished by treatment with the NCXrm blockers SEA0400, KB-R7943, or SN-6.
View Article and Find Full Text PDFElectromagnetic fields (EMF) in the radio frequency energy (RFE) range can affect cells at the molecular level. Here we report a technology that can record the specific RFE signal of a given molecule, in this case the siRNA of epidermal growth factor receptor (EGFR). We demonstrate that cells exposed to this EGFR siRNA RFE signal have a 30-70% reduction of EGFR mRNA expression and ~60% reduction in EGFR protein expression vs.
View Article and Find Full Text PDFControl of blood flow distribution and tissue homeostasis depend on the tight regulation of and coordination between the microvascular network and circulating blood cells. Channels formed by connexins or pannexins that connect the intra- and extracellular compartments allow the release of paracrine signals, such as ATP and prostaglandins, and thus play a central role in achieving fine regulation and coordination of vascular function. This review focuses on vascular connexin hemichannels and pannexin channels.
View Article and Find Full Text PDFObjective: First, to demonstrate that B-level evidence exists for the use of hyperbaric oxygen therapy (HBOT) as an effective treatment in mild to moderate traumatic brain injury/persistent postconcussion syndrome (mTBI/PPCS). Second, to alert readers and researchers that currently used pressurized air controls (≥21% O2, >1.0 ATA) are therapeutically active and cannot be utilized as sham controls without further validation.
View Article and Find Full Text PDFThe authors review the diagnostic overlap that exists between posttraumatic stress disorder (PTSD) and traumatic brain injury (TBI). Achieving the correct diagnosis is much more difficult and the potential to inappropriately treat patients is greater than most physicians realize. The need to properly diagnose and select appropriate treatment strategies is essential, especially with TBI cases.
View Article and Find Full Text PDFUndersea Hyperb Med
September 2015
The current debate surrounding the use of hyperbaric oxygen (HBO2) for neurological indications, specifically mild to moderate chronic traumatic brain injury (mTBI) and post-concussion syndrome (PCS), is mired in confusion due to the use of non-validated controls and an unfamiliarity by many practitioners of HBO2 therapy with the experimental literature. In the past 40 years, the use of an air sham (21% oxygen, 1.14-1.
View Article and Find Full Text PDFNeuronal activity must be tightly coordinated with blood flow to keep proper brain function, which is achieved by a mechanism known as neurovascular coupling. Then, an increase in synaptic activity leads to a dilation of local parenchymal arterioles that matches the enhanced metabolic demand. Neurovascular coupling is orchestrated by astrocytes.
View Article and Find Full Text PDFThe microvascular network of the microcirculation works in tight communication with surrounding tissues to control blood supply and exchange of solutes. In cerebral circulation, microvascular endothelial cells constitute a selective permeability barrier that controls the environment of parenchymal brain tissue, which is known as the blood-brain barrier (BBB). Connexin- and pannexin-formed channels (gap junctions and hemichannels) play a central role in the coordination of endothelial and smooth muscle cell function and connexin-mediated signaling in endothelial cells is essential in the regulation of BBB permeability.
View Article and Find Full Text PDFBackground/aims: Endothelial nitric oxide synthase (eNOS) is associated with caveolin-1 (Cav-1) in plasma membrane. We tested the hypothesis that eNOS activation by shear stress in resistance vessels depends on synchronized phosphorylation, dissociation from Cav-1 and translocation of the membrane-bound enzyme to Golgi and cytosol.
Methods: In isolated, perfused rat arterial mesenteric beds, we evaluated the effect of changes in flow rate (2-10 ml/min) on nitric oxide (NO) production, eNOS phosphorylation at serine 1177, eNOS subcellular distribution and co-immunoprecipitation with Cav-1, in the presence or absence of extracellular Ca(2+).
Proc Natl Acad Sci U S A
October 2013