July 18, 2011 Every year, more than 800,000 children in impoverished countries die from diarrhea and vomiting caused by rotavirus and norovirus -- 'winter vomiting disease'. Researchers at Linköping University and other institutions have now discovered how vomiting develops in viral infections and have found a way to quickly treat these children and others in the risk zone for dehydration.
It is well known that viruses like rotavirus and norovirus are behind the majority of stomach infections. But it was unclear how vomiting developed, and the treatments available were oral fluid replacement and intravenous drips to prevent dehydration of the body.
Now a research team, led by Professor Lennart Svensson at Linköping University, has produced results that show for the first time how the viruses give rise to vomiting. A new treatment is being proposed, with a previously established medicine that is used for nausea and vomiting in cancer treatments. The results are to be published in the online journal PLoS Pathogens.
What researchers have found is that the viral infection and the toxin excreted from infected cells stimulate a type of sensory cell called entrochromaffin cells in the walls of the digestive tract. These cells can communicate with the brain via the vagus nerve.
"We have shown that the viral toxin stimulates the cells to release serotonin, a signalling substance that in turn activates the brain's vomiting centre," says Maria Hagbom, laboratory engineer in the Department of Molecular Virology at LiU and the chief author of the article in PLoS Pathogens.
The pattern was studied both in cell cultures, where the researchers demonstrated that the viral toxin caused a release of serotonin, and in mice, where it was seen that a rotavirus infection in the intestines activated the areas in the brain where the vomiting centre is located.
Cancer patients who suffer from vomiting in connection with cytostatics are treated today with a medicine that blocks serotonin receptors. The researchers' hypothesis is that the same medicine can relieve vomiting caused by rotavirus and norovirus.
"The treatment often offered today is fluid replacement, an oral saline and sugar solution which is troublesome with frequent vomiting. Since intense vomiting makes it difficult to retain fluid, this often leads to the patient having to be treated with a drip. Through restricting vomiting with this medicine, many lives in developing countries could be saved," says Lennart Svensson, Professor of Molecular Virology at LiU.
Comprehensive clinical testing is now being planned in Brazil on children infected with rotavirus or norovirus. The hope is that it will start up this fall. If the results are positive, the medicine may come into clinical use in the near future, since it is already approved and established. Beside the clinical study, the research group has established an animal model that is entirely new to Europe for studying illness mechanisms.
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- Marie Hagbom, Claudia Istrate, David Engblom, Thommie Karlsson, Jesus Rodriguez-Diaz, Javier Buesa, John A. Taylor, Vesa-Matti Loitto, Karl-Eric Magnusson, Håkan Ahlman, Ove Lundgren, Lennart Svensson. Rotavirus Stimulates Release of Serotonin (5-HT) from Human Enterochromaffin Cells and Activates Brain Structures Involved in Nausea and Vomiting. PLoS Pathogens, 2011; 7 (7): e1002115 DOI: 10.1371/journal.ppat.1002115
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