Brain's on-off thirst switch identified

January 27, 2015

Brains on-off

Washington, Jan 27: Scientists have identified neurons that trigger our sense of thirst and those that turn it off.

For years, researchers have suspected that thirst is regulated by neurons in the subfornical organ (SFO), in the hypothalamus. But it has been difficult to pinpoint exactly which neurons are involved.

“When researchers used electrical current to stimulate different parts of the SFO of mice, they got confusing results,” said lead author Yuki Oka, a postdoctoral research scientist in the laboratory of Charles S Zuker, a Howard Hughes Medical Institute Investigator at Columbia University Medical Center (CUMC).

The CUMC team hypothesised that there are at least two types of neurons in the SFO, including ones that drive thirst and others that suppress it.

“Those electrostimulation experiments were probably activating both types of neurons at once, so they were bound to get conflicting results,” said Oka.

To test their hypothesis, Oka and Zuker turned to optogenetics, a more precise technique for controlling brain activity. With optogenetics, researchers can control specific sets of neurons in the brain after inserting light-activated molecules into them.

Shining light onto these molecules turns on the neurons without affecting other types of neurons nearby.

These “mind-control” experiments revealed two types of neurons in the SFO that control thirst: CAMKII neurons, which turn thirst on, and VGAT neurons, which turn it off.

When the researchers turned on CAMK11 neurons, mice immediately began to seek water and to drink intensively.

This behaviour was as strong in well-hydrated mice as in dehydrated ones. Once the neurons were shut off – by turning off the light – the mice immediately stopped drinking.

The researchers also found that light-stimulation of the CAMKII neurons did not induce feeding behaviour. In addition, light-induced thirst was specific for water and did not increase the animals’ consumption of other fluids, including glycerol and honey.

Similar experiments with VGAT neurons showed that these neurons act to turn off thirst. When the researchers turned on these neurons with light, dehydrated mice immediately stopped drinking, even if they were drinking water.

“Together, these findings show that the SFO is a dedicated brain system for thirst,” said Oka.

“The SFO is one of few neurological structures that is not blocked by the blood-brain barrier – it’s completely exposed to the general circulation,” said Oka.

“This raises the possibility that it may be possible to develop drugs for conditions related to thirst,” Oka added.

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News Network
February 26,2020

New York, Feb 26:  A new wearable sensor that works in conjunction with artificial intelligence (AI) technology could help doctors remotely detect critical changes in heart failure patients days before a health crisis occurs, says a study.

The researchers said the system could eventually help avert up to one in three heart failure readmissions in the weeks following initial discharge from the hospital and help patients sustain a better quality of life.

"This study shows that we can accurately predict the likelihood of hospitalisation for heart failure deterioration well before doctors and patients know that something is wrong," says the study's lead author Josef Stehlik from University of Utah in the US.

"Being able to readily detect changes in the heart sufficiently early will allow physicians to initiate prompt interventions that could prevent rehospitalisation and stave off worsening heart failure," Stehlik added.

According to the researchers, even if patients survive, they have poor functional capacity, poor exercise tolerance and low quality of life after hospitalisations.

"This patch, this new diagnostic tool, could potentially help us prevent hospitalizations and decline in patient status," Stehlik said.

For the findings, published in the journal Circulation: Heart Failure, the researchers followed 100 heart failure patients, average age 68, who were diagnosed and treated at four veterans administration (VA) hospitals in Utah, Texas, California, and Florida.

After discharge, participants wore an adhesive sensor patch on their chests 24 hours a day for up to three months.

The sensor monitored continuous electrocardiogram (ECG) and motion of each subject.

This information was transmitted from the sensor via Bluetooth to a smartphone and then passed on to an analytics platform, developed by PhysIQ, on a secure server, which derived heart rate, heart rhythm, respiratory rate, walking, sleep, body posture and other normal activities.

Using artificial intelligence, the analytics established a normal baseline for each patient. When the data deviated from normal, the platform generated an indication that the patient's heart failure was getting worse.

Overall, the system accurately predicted the impending need for hospitalization more than 80 per cent of the time.

On average, this prediction occurred 10.4 days before a readmission took place (median 6.5 days), the study said.

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News Network
July 10,2020

Toronto, Jul 10: Pasteurising breast milk at 62.5 degrees Celsius for 30 minutes inactivates the SARS-CoV-2 virus that causes Covid-19, making it safe for consumption by babies, a study claims.

According to the research published in the Canadian Medical Association Journal, current advice for women with Covid-19 is to continue to breastfeed their own infants.

In Canada, it is standard care to provide pasteurised breast milk to very-low-birth-weight babies in hospital until their own mother's milk supply is adequate, the researchers said.

"In the event that a woman who is Covid-19-positive donates human milk that contains SARS-CoV-2, whether by transmission through the mammary gland or by contamination through respiratory droplets, skin, breast pumps and milk containers, this method of pasteurisation renders milk safe for consumption," said Sharon Unger, a professor at the University of Toronto in Canada.

The Holder method, a technique used to pasteurise milk in all Canadian milk banks at 62.5 degrees Celsius for 30 minutes, is effective at neutralising viruses such as HIV, hepatitis and others that are known to be transmitted through human milk, the researchers said.

In the latest study, the researchers spiked human breast milk with a viral load of SARS-CoV-2 and tested samples that either sat at room temperature for 30 minutes or were warmed to 62.5 degrees Celsius for 30 minutes.

They then measured for active virus, finding that the virus in the pasteurised milk was inactivated after heating.

More than 650 human breast milk banks around the world use the Holder method to ensure a safe supply of milk for vulnerable infants, the researchers said.

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Agencies
June 17,2020

Leading physicians are celebrating a small dose of good news that arrived Tuesday about dexamethasone, a cheap and widely used steroid shown to be able to save lives among COVID-19 patients, but also cautioning against releasing study results by press release during a global health emergency, like in the case of the latest dexamethasone study by University of Oxford.

"It will be great news if dexamethasone, a cheap steroid, really does cut deaths by one-third in ventilated patients with COVID19, but after all the retractions and walk backs, it is unacceptable to tout study results by press release without releasing the paper", Atul Gawande, surgeon and CEO of Haven Healthcare, tweeted.

"Bottom line is, good news," Dr. Fauci, America's foremost infectious diseases expert told a US newswire on Tuesday, soon after the dexamethasone results were announced in the UK.

Fauci, who has long championed the therapeutics-first view said that dexamethasone is a "significant improvement" in the available therapeutic options currently available.

On Medical Twitter and Facebook, doctors broadly agree that dexamethasone use aligns well with the way COVID19 attacks the body's immune system. Fauci said the results in the Oxford study make "perfect sense" in that context.

"We should see the number of people who actually survive go up, if the study holds up," virologist and epidemiologist Dr. Joseph Fair told a television network.

Global coronavirus cases crossed 8 million on Tuesday. In the US, Texas and Florida are facing a new wave of cases after lifting lockdown orders earlier than medical experts recommended. Amidst the relentless graph upwards, the dexamethasone study results injected hope for better survival rates among those most seriously ill.

World Health Organization chief scientist Soumya Swaminathan welcomed the results from the randomised control trial.

Dr Eugene Gu, Founder and CEO of CoolQuit tweeted that he is "genuinely impressed" with the UK dexamethasone trial. This may be a "game changer", he wrote.

"There's no conflict of interest as dexamethasone is a generic steroid. The mechanism of action makes sense because steroids can reduce cytokine storms and overactive immune systems that makes COVID-19 so deadly. The number needed to treat is 8 ventilated patients which is great."

The Oxford study found that dexamethasone reduced deaths by 35 percent in patients who needed treatment with breathing machines and by 20 percent in those only needing supplemental oxygen. Dexamethasone was one of 5 drugs studied in a large clinical trial in the United Kingdom named RECOVERY, short for Randomised Evaluation of COVID-19 Therapy.

Peter Horby, chief investigator of the University of Oxford clinical trial, said dexamethasone is the first drug to be shown to improve survival in COVID-19. Details of the study have not been released. The trial organisers said they made their announcement via a news release because of "the public health importance of these results." According to Horby's public comments, there was a lot of initial resistance to studying steroids.

During the study, 2,104 patients were randomly selected to be given 6 milligrams of dexamethasone once a day (either by mouth or by intravenous injection) for 10 days. That group was compared with 4,321 patients who received the usual care alone.

Researchers estimated that dexamethasone would prevent one death for every eight patients treated while on ventilators and one for every 25 patients on extra oxygen alone.

UK experts have called the study results a breakthrough in the fight against the virus. The researchers have promised they would publish the results soon.

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