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!
New gene catalog of ocean microbiome reveals surprises
18.08.2017 | University of Hawaii at Manoa
Organ Crosstalk: Fatty Liver Can Cause Damage to Other Organs
18.08.2017 | Deutsches Zentrum für Diabetesforschung
Whether you call it effervescent, fizzy, or sparkling, carbonated water is making a comeback as a beverage. Aside from quenching thirst, researchers at the University of Illinois at Urbana-Champaign have discovered a new use for these "bubbly" concoctions that will have major impact on the manufacturer of the world's thinnest, flattest, and one most useful materials -- graphene.
As graphene's popularity grows as an advanced "wonder" material, the speed and quality at which it can be manufactured will be paramount. With that in mind,...
Physicists at the University of Bonn have managed to create optical hollows and more complex patterns into which the light of a Bose-Einstein condensate flows. The creation of such highly low-loss structures for light is a prerequisite for complex light circuits, such as for quantum information processing for a new generation of computers. The researchers are now presenting their results in the journal Nature Photonics.
Light particles (photons) occur as tiny, indivisible portions. Many thousands of these light portions can be merged to form a single super-photon if they are...
For the first time, scientists have shown that circular RNA is linked to brain function. When a RNA molecule called Cdr1as was deleted from the genome of mice, the animals had problems filtering out unnecessary information – like patients suffering from neuropsychiatric disorders.
While hundreds of circular RNAs (circRNAs) are abundant in mammalian brains, one big question has remained unanswered: What are they actually good for? In the...
An experimental small satellite has successfully collected and delivered data on a key measurement for predicting changes in Earth's climate.
The Radiometer Assessment using Vertically Aligned Nanotubes (RAVAN) CubeSat was launched into low-Earth orbit on Nov. 11, 2016, in order to test new...
A study led by scientists of the Max Planck Institute for the Structure and Dynamics of Matter (MPSD) at the Center for Free-Electron Laser Science in Hamburg presents evidence of the coexistence of superconductivity and “charge-density-waves” in compounds of the poorly-studied family of bismuthates. This observation opens up new perspectives for a deeper understanding of the phenomenon of high-temperature superconductivity, a topic which is at the core of condensed matter research since more than 30 years. The paper by Nicoletti et al has been published in the PNAS.
Since the beginning of the 20th century, superconductivity had been observed in some metals at temperatures only a few degrees above the absolute zero (minus...
16.08.2017 | Event News
04.08.2017 | Event News
26.07.2017 | Event News
18.08.2017 | Life Sciences
18.08.2017 | Physics and Astronomy
18.08.2017 | Information Technology