17 research outputs found
Определение параметров колебаний в электроприводах постоянного тока с импульсным регулированием скорости
AbstractA comprehensive experimental approach has been used to assess the interrelation of CO2-mediated chemical reactions and transport properties in pelitic rocks. Sorption values on shale samples (P<20 MPa, 50 ∘C) were high with maximum amounts of ∼44 kg/t. These capacities did not correlate with the organic carbon content, indicating sorption on and/or reaction with mineral components. Further, crushed shale samples were exposed to CO2 in the presence of water at 15 MPa and 50 ∘C for different time periods, showing significant changes in mineral composition. Reaction equilibrium was reached within periods of less than a month. Some of the caprock lithotypes could represent a significant sink for CO2 deposited in the subsurface and could reduce the risk of leakage to the surface
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Chronic BDNF simultaneously inhibits and unmasks superficial dorsal horn neuronal activity.
Funder: Department of Anesthesiology and Critical Care Medicine, University of New Mexico Health Sciences CenterFunder: Canadian Institutes of Health Research; doi: http://dx.doi.org/10.13039/501100000024Brain-derived neurotrophic factor (BDNF) is critically involved in the pathophysiology of chronic pain. However, the mechanisms of BDNF action on specific neuronal populations in the spinal superficial dorsal horn (SDH) requires further study. We used chronic BDNF treatment (200 ng/ml, 5-6 days) of defined-medium, serum-free spinal organotypic cultures to study intracellular calcium ([Ca2+]i) fluctuations. A detailed quantitative analysis of these fluctuations using the Frequency-independent biological signal identification (FIBSI) program revealed that BDNF simultaneously depressed activity in some SDH neurons while it unmasked a particular subpopulation of 'silent' neurons causing them to become spontaneously active. Blockade of gap junctions disinhibited a subpopulation of SDH neurons and reduced BDNF-induced synchrony in BDNF-treated cultures. BDNF reduced neuronal excitability assessed by measuring spontaneous excitatory postsynaptic currents. This was similar to the depressive effect of BDNF on the [Ca2+]i fluctuations. This study reveals novel regulatory mechanisms of SDH neuronal excitability in response to BDNF
Sensory neuron–derived NaV1.7 contributes to dorsal horn neuron excitability
Expression of the voltage-gated sodium channel NaV1.7 in sensory neurons is required for pain sensation. We
examined the role of NaV1.7 in the dorsal horn of the spinal cord using an epitope-tagged NaV1.7 knock-in mouse.
Immuno–electron microscopy showed the presence of NaV1.7 in dendrites of superficial dorsal horn neurons, despite
the absence of mRNA. Rhizotomy of L5 afferent nerves lowered the levels of NaV1.7 in the dorsal horn. Peripheral
nervous system–specific NaV1.7 null mutant mice showed central deficits, with lamina II dorsal horn tonic
firing neurons more than halved and single spiking neurons more than doubled. NaV1.7 blocker PF05089771 diminished
excitability in dorsal horn neurons but had no effect on NaV1.7 null mutant mice. These data demonstrate
an unsuspected functional role of primary afferent neuron-generated NaV1.7 in dorsal horn neurons and an
expression pattern that would not be predicted by transcriptomic analysis
Plant-derived natural products targeting ion channels for pain
Chronic pain affects approximately one-fifth of people worldwide and reduces quality of life and in some cases, working ability. Ion channels expressed along nociceptive pathways affect neuronal excitability and as a result modulate pain experience. Several ion channels have been identified and investigated as potential targets for new medicines for the treatment of a variety of human diseases, including chronic pain. Voltage-gated channels Na+ and Ca2+ channels, K+ channels, transient receptor potential channels (TRP), purinergic (P2X) channels and acid-sensing ion channels (ASICs) are some examples of ion channels exhibiting altered function or expression in different chronic pain states. Pharmacological approaches are being developed to mitigate dysregulation of these channels as potential treatment options. Since natural compounds of plant origin exert promising biological and pharmacological properties and are believed to possess less adverse effects compared to synthetic drugs, they have been widely studied as treatments for chronic pain for their ability to alter the functional activity of ion channels. A literature review was conducted using Medline, Google Scholar and PubMed, resulted in listing 79 natural compounds/extracts that are reported to interact with ion channels as part of their analgesic mechanism of action. Most in vitro studies utilized electrophysiological techniques to study the effect of natural compounds on ion channels using primary cultures of dorsal root ganglia (DRG) neurons. In vivo studies concentrated on different pain models and were conducted mainly in mice and rats. Proceeding into clinical trials will require further study to develop new, potent and specific ion channel modulators of plant origin