Sepsis, the body's response to severe infections, kills more people than breast cancer, prostate cancer and HIV/AIDS combined. On average, 30 percent of those diagnosed with sepsis die.
Histopathological analyses of liver and spleen tissue 48 hours after infection exhibited fibrin thrombi and empty vessels (open arrows) indicative of thromboembolic occlusions. Functioning blood vessels containing red blood cells are also denoted (closed arrows). Pyknotic bodies indicating cell death are marked (asterisks).
A new study conducted by Jamey Marth, director of UC Santa Barbara's Center for Nanomedicine and professor of the Sanford-Burnham Medical Research Institute, reports a new method to increase survival in sepsis. The results appear today in the Proceedings of the National Academy of Sciences.
Building on earlier work in which Marth's team revealed the biological purpose of the Ashwell-Morell receptor (AMR) in the liver, the new discovery not only describes the AMR's protective mechanism, but also outlines a way to leverage it for therapeutic use. Sepsis often triggers widespread blood coagulation and thrombosis, which can lead to organ failure and death.
The researchers found that the AMR protects the host by the rapid removal of the prothrombotic components normally present in the bloodstream, including platelets and specific coagulation factors that contribute to the formation of blood clots. The study elucidates this mechanism of AMR function in mitigating the lethal effects of excessive blood coagulation and thrombosis in sepsis.
The key is neuraminidase, an enzyme that is present in many pathogenic microorganisms, such as Streptococcus pneumoniae, the bacteria used in this study, which remains one of the top five causes of death worldwide. Pathogens use neuraminidase to get into cells, but once the pathogen enters the bloodstream, the enzyme then remodels the surface of platelets and other glycoproteins in circulation. This remodeling signals the AMR to remove those platelets and coagulation factors before they have a chance to contribute to the lethal coagulopathy of sepsis.
"It's a highly conserved protective mechanism never before identified," said Marth, who is also Carbon Professor of Biochemistry and Molecular Biology and Mellichamp Professor of Systems Biology at UCSB. "The host has evolved this protective mechanism over millions of years as a way to compensate for the lethal impact of the pathogen on our coagulation system."
The scientists wondered what would happen if they could pre-activate and augment AMR function in the early phases of sepsis. To answer that question, they infected mice with Streptococcus pneumoniae and then gave them a single dose of neuraminidase. "We were able to increase survival twofold," said Marth. "It's remarkable, and because we see the same mechanism active in human sepsis there is excitement by the potential of this approach to save millions of lives."
In teasing out the details of the AMR's protective mechanism, Marth and his colleagues learned that the receptor has the capability to selectively identify and remove certain blood components that could harm the host if they contributed to blood clotting in sepsis.
Although some scientists have suggested that little may be gained from research on sepsis in non-human species, the study by the Marth team discloses a mechanism of host protection that is conserved through mammalian evolution and which can be easily manipulated. The fact that this mechanism is imperceptible to studies of genomic variation and gene expression may explain why others have not discovered it earlier. "Much of biomedical research is focused on the gene. In our research, it was the study of metabolism that provided the key," explained Marth.
"Because it appears that the same protective mechanism exists in humans, investors have already contacted us about moving this forward into clinical trials," Marth said. "It's estimated that 50 to 100 million people around the world have sepsis each year, and we can now imagine a simple effective treatment consisting of a non-refrigerated enzyme mixed with saline, placed in a syringe and injected intravenously. This has the potential to translate into saved lives among those in the developed and undeveloped world."
Julie Cohen | EurekAlert!
Modern genetic sequencing tools give clearer picture of how corals are related
17.08.2017 | University of Washington
The irresistible fragrance of dying vinegar flies
16.08.2017 | Max-Planck-Institut für chemische Ökologie
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
17.08.2017 | Physics and Astronomy
17.08.2017 | Earth Sciences
17.08.2017 | Physics and Astronomy