The short-acting gas helps unglue hemoglobin molecules that stick together, forming long chains that ultimately deform red blood cells and prompting a cellular pileup in small blood vessels and pain, said Dr. C. Alvin Head, Chairman of GHSU’s Department of Anesthesiology.
The findings get scientists closer to understanding why red blood cells sickle and potentially to a easy-to-use, non-addictive treatment that helps avoid it, said Dr. Tohru Ikuta, GHSU molecular hematologist.
Hydroxyurea, which prompts the body to make more fetal hemoglobin which cannot sickle, is currently the only approved therapy for sickle cell. Patients with recurring pain crises typically must take increasingly higher doses of stronger narcotics to deal with the pain.
Head and his colleagues envision instead an inhaler like asthmatics use that enables them to breathe in nitric oxide when they feel a pain crisis coming on. “Drugs just mask the symptoms,” Head said. “We have mounting evidence that nitric oxide directly addresses the source of pain crises to help patients avoid them.”
They’ve shown in a small patient sample that inhaling nitric oxide appears safe and effective. The study of 18 patients in Atlanta, Chicago and Detroit published in 2010 in the American Journal of Hematology showed that the half who inhaled nitric oxide for four hours had better pain control than those receiving only the standard self-administered morphine.
The new study examined nitric oxide’s impact from many angles and showed that it appears to disperse dense, solid chains of hemoglobin troublemakers. Once a significant number of hemoglobin molecules stick together, it causes red blood cells to distort from their natural round shape that easily maneuvers blood vessels to a sickle-shape. At that point, red blood cells also become uncharacteristically sticky.
They found nitric oxide reduced the length of the unnatural hemoglobin strands, made the strands more fragile and, using a high-powered confocal microscope, they could see it also helped cells regain a more normal shape. Studies were done on human cells in vitro.
Next steps include fine-tuning the dose and learning more about why red blood cells become sticky. Head notes that with a gas, it’s a lot more tricky to determine how much drug gets into the blood than with an oral or intravenous delivery. They already have evidence that in sickle cell disease red and white blood cells stick together, which they should not.
They believe their findings about how these cells clog up vessels will have broad applications for a number of clot-based conditions, including the increased clot risk that follows surgery. “Really what we are learning is the basic understanding of early clot formation,” Head said.
Earlier this year, GHSU scientists reported in Blood that a new compound, an aptamer, developed by Archemix Corporation in Cambridge, Mass., also appears to prevent cellular pileups by occupying sticky receptors lining the walls of small blood vessels where sickle-shaped red blood cells and white blood cells can stick. That study, led by Dr. Diana R. Gutsaeva, GHSU physiologist and molecular biologist, points toward another potential sickle cell therapy.
Toni Baker | EurekAlert!
Toward a 'smart' patch that automatically delivers insulin when needed
18.01.2017 | American Chemical Society
127 at one blow...
18.01.2017 | Stiftung Zoologisches Forschungsmuseum Alexander Koenig, Leibniz-Institut für Biodiversität der Tiere
Yersiniae cause severe intestinal infections. Studies using Yersinia pseudotuberculosis as a model organism aim to elucidate the infection mechanisms of these...
Researchers from the University of Hamburg in Germany, in collaboration with colleagues from the University of Aarhus in Denmark, have synthesized a new superconducting material by growing a few layers of an antiferromagnetic transition-metal chalcogenide on a bismuth-based topological insulator, both being non-superconducting materials.
While superconductivity and magnetism are generally believed to be mutually exclusive, surprisingly, in this new material, superconducting correlations...
Laser-driving of semimetals allows creating novel quasiparticle states within condensed matter systems and switching between different states on ultrafast time scales
Studying properties of fundamental particles in condensed matter systems is a promising approach to quantum field theory. Quasiparticles offer the opportunity...
Among the general public, solar thermal energy is currently associated with dark blue, rectangular collectors on building roofs. Technologies are needed for aesthetically high quality architecture which offer the architect more room for manoeuvre when it comes to low- and plus-energy buildings. With the “ArKol” project, researchers at Fraunhofer ISE together with partners are currently developing two façade collectors for solar thermal energy generation, which permit a high degree of design flexibility: a strip collector for opaque façade sections and a solar thermal blind for transparent sections. The current state of the two developments will be presented at the BAU 2017 trade fair.
As part of the “ArKol – development of architecturally highly integrated façade collectors with heat pipes” project, Fraunhofer ISE together with its partners...
At TU Wien, an alternative for resource intensive formwork for the construction of concrete domes was developed. It is now used in a test dome for the Austrian Federal Railways Infrastructure (ÖBB Infrastruktur).
Concrete shells are efficient structures, but not very resource efficient. The formwork for the construction of concrete domes alone requires a high amount of...
10.01.2017 | Event News
09.01.2017 | Event News
05.01.2017 | Event News
18.01.2017 | Power and Electrical Engineering
18.01.2017 | Materials Sciences
18.01.2017 | Life Sciences