Nicotine normalises brain activity in schizophrenia patients

January 25, 2017

Washington, Jan 25: A steady stream of nicotine normalises genetically-induced impairments in brain activity associated with schizophrenia, according to a new study that could lead to new non-addictive, nicotine-based treatments for the 51 million people worldwide who suffer from the disease.

BrainThe finding sheds light on what causes the disease and why those who have it tend to smoke heavily.

It could also potentially have applications for treating addiction, Attention Deficit Hyperactivity Disorder, Bipolar disorder and other psychiatric conditions.

"Our study provides compelling biological evidence that a specific genetic variant contributes to risk for schizophrenia, defines the mechanism responsible for the effect and validates that nicotine improves that deficit," said Jerry Stitzel, researcher at the Institute for Behavioural Genetics (IBG) in the US.

The study found that when mice with schizophrenic characteristics were given nicotine daily, their sluggish brain activity increased within two days. Within one week it had normalised.

"Basically the nicotine is compensating for a genetically determined impairment. No one has ever shown that before," said Stitzel.

The scientists set out to explore the underlying causes of "hypofrontality"?a reduction of neuronal firing in the prefrontal cortex of the brain.

Hypofrontality is believed to be the root cause of many of the signature cognitive problems experienced by schizophrenics, including trouble paying attention, remembering things, making decisions and understanding verbal explanations.

Previous genome-wide association studies have suggested that people with a variation in a gene called CHRNA5 are more likely to have schizophrenia, but the mechanism for that association has remained unclear. People with that variant are also more likely to smoke.

Eighty to 90 per cent of people with schizophrenia smoke and most are very heavy smokers, a fact that has long led researchers to suspect they are self-medicating.

The research team first took mice with the CHRNA5 gene variant and used state-of-the-art brain imaging technologies to see if they had hypofrontality.

Then they conducted behavioural tests to see if the mice shared key characteristics of schizophrenics, like being unable to suppress a startle response and being averse to social interaction.

The results validated that the gene variant likely plays a role in schizophrenia by causing hypofrontality, said Stitzel.

Nicotine appeared to reverse this in the mice, normalising brain activity by acting on nicotinic receptors in regions of the brain key to healthy cognitive function.

The study appears in the journal Nature Medicine.

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Agencies
March 27,2020

New Delhi, Mar 27: The Centre has restricted sale and distribution of "hydroxychloroquine" declaring it as an essential drug to treat the COVID-19 patients and meet the requirements of emergency arising due to the pandemic.

The Ministry of Health and Family Welfare on Thursday made the announcement making it clear that the order "shall come into force on the date of its publication in the official Gazette".

In the order, the government declared that the Central government is "satisfied that the drug hydroxychloroquine is essential to meet the requirements of emergency arising due to pandemic COVID-19 and in the public interest, it is necessary and expedient to regulate and restrict the sale and distribution of the drug 'hydroxychloroquine' and preparation based thereon for preventing their misuse".

"Now, therefore, in exercise of the powers conferred by Section 26B of the Drugs and Cosmetics Act, 1940 (23 of 1940), the Central government hereby directs that sale by retail of any preparation containing the drug Hydroxychloroquine shall be in accordance with the conditions for sale of drugs specified in Schedule H1 to the Drugs and Cosmetics Rules, 1945."

The order came at a time when the novel coronavirus claimed 16 lives and infected over 600 people across India.

The announcement regarding ban of sale and distribution of the drug was made by the government earlier but it issued an official Gazette notification on Thursday signalling that hydroxychloroquine -- an anti-Malaria drug -- will work as a medicine for treating coronavirus infected patients as well.

Recently, the national task force for COVID-19 constituted by Indian Council for Medical Research (ICMR) has recommended hydroxy-chloroquine as a preventive medication.

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International New York Times
July 7,2020

The coronavirus can stay aloft for hours in tiny droplets in stagnant air, infecting people as they inhale, mounting scientific evidence suggests.

This risk is highest in crowded indoor spaces with poor ventilation, and may help explain superspreading events reported in meatpacking plants, churches and restaurants.

It’s unclear how often the virus is spread via these tiny droplets, or aerosols, compared with larger droplets that are expelled when a sick person coughs or sneezes, or transmitted through contact with contaminated surfaces, said Linsey Marr, an aerosol expert at Virginia Tech.

Follow latest updates on the Covid-19 pandemic here

Aerosols are released even when a person without symptoms exhales, talks or sings, according to Marr and more than 200 other experts, who have outlined the evidence in an open letter to the World Health Organization.

What is clear, they said, is that people should consider minimizing time indoors with people outside their families. Schools, nursing homes and businesses should consider adding powerful new air filters and ultraviolet lights that can kill airborne viruses.

What does it mean for a virus to be airborne?

For a virus to be airborne means that it can be carried through the air in a viable form. For most pathogens, this is a yes-no scenario. HIV, too delicate to survive outside the body, is not airborne. Measles is airborne, and dangerously so: It can survive in the air for up to two hours.

For the coronavirus, the definition has been more complicated. Experts agree that the virus does not travel long distances or remain viable outdoors. But evidence suggests it can traverse the length of a room and, in one set of experimental conditions, remain viable for perhaps three hours.

How are aerosols different from droplets?

Aerosols are droplets, droplets are aerosols — they do not differ except in size. Scientists sometimes refer to droplets fewer than 5 microns in diameter as aerosols. (By comparison, a red blood cell is about 5 microns in diameter; a human hair is about 50 microns wide.)

From the start of the pandemic, the WHO and other public health organizations have focused on the virus’s ability to spread through large droplets that are expelled when a symptomatic person coughs or sneezes.

These droplets are heavy, relatively speaking, and fall quickly to the floor or onto a surface that others might touch. This is why public health agencies have recommended maintaining a distance of at least 6 feet from others, and frequent hand washing.

But some experts have said for months that infected people also are releasing aerosols when they cough and sneeze. More important, they expel aerosols even when they breathe, talk or sing, especially with some exertion.

Scientists know now that people can spread the virus even in the absence of symptoms — without coughing or sneezing — and aerosols might explain that phenomenon.

Because aerosols are smaller, they contain much less virus than droplets do. But because they are lighter, they can linger in the air for hours, especially in the absence of fresh air. In a crowded indoor space, a single infected person can release enough aerosolized virus over time to infect many people, perhaps seeding a superspreader event.

For droplets to be responsible for that kind of spread, a single person would have to be within a few feet of all the other people, or to have contaminated an object that everyone else touched. All that seems unlikely to many experts: “I have to do too many mental gymnastics to explain those other routes of transmission compared to aerosol transmission, which is much simpler,” Marr said.

Can I stop worrying about physical distancing and washing my hands?

Physical distancing is still very important. The closer you are to an infected person, the more aerosols and droplets you may be exposed to. Washing your hands often is still a good idea.

What’s new is that those two things may not be enough. “We should be placing as much emphasis on masks and ventilation as we do with hand washing,” Marr said. “As far as we can tell, this is equally important, if not more important.”

Should I begin wearing a hospital-grade mask indoors? And how long is too long to stay indoors?

Health care workers may all need to wear N95 masks, which filter out most aerosols. At the moment, they are advised to do so only when engaged in certain medical procedures that are thought to produce aerosols.

For the rest of us, cloth face masks will still greatly reduce risk, as long as most people wear them. At home, when you’re with your own family or with roommates you know to be careful, masks are still not necessary. But it is a good idea to wear them in other indoor spaces, experts said.

As for how long is safe, that is frustratingly tough to answer. A lot depends on whether the room is too crowded to allow for a safe distance from others and whether there is fresh air circulating through the room.

What does airborne transmission mean for reopening schools and colleges?

This is a matter of intense debate. Many schools are poorly ventilated and are too poorly funded to invest in new filtration systems. “There is a huge vulnerability to infection transmission via aerosols in schools,” said Don Milton, an aerosol expert at the University of Maryland.

Most children younger than 12 seem to have only mild symptoms, if any, so elementary schools may get by. “So far, we don’t have evidence that elementary schools will be a problem, but the upper grades, I think, would be more likely to be a problem,” Milton said.

College dorms and classrooms are also cause for concern.

Milton said the government should think of long-term solutions for these problems. Having public schools closed “clogs up the whole economy, and it’s a major vulnerability,” he said.

“Until we understand how this is part of our national defense, and fund it appropriately, we’re going to remain extremely vulnerable to these kinds of biological threats.”

What are some things I can do to minimize the risks?

Do as much as you can outdoors. Despite the many photos of people at beaches, even a somewhat crowded beach, especially on a breezy day, is likely to be safer than a pub or an indoor restaurant with recycled air.

But even outdoors, wear a mask if you are likely to be close to others for an extended period.

When indoors, one simple thing people can do is to “open their windows and doors whenever possible,” Marr said. You can also upgrade the filters in your home air-conditioning systems, or adjust the settings to use more outdoor air rather than recirculated air.

Public buildings and businesses may want to invest in air purifiers and ultraviolet lights that can kill the virus. Despite their reputation, elevators may not be a big risk, Milton said, compared with public bathrooms or offices with stagnant air where you may spend a long time.

If none of those things are possible, try to minimize the time you spend in an indoor space, especially without a mask. The longer you spend inside, the greater the dose of virus you might inhale.

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News Network
May 13,2020

California, May 13: A fasting-mimicking diet could be more effective at treating some types of cancer when combined with vitamin C, suggests a new study conducted by the scientists from USC and the IFOM Cancer Institute in Milan.

In studies on mice, researchers found that the combination delayed tumour progression in multiple mouse models of colorectal cancer; in some mice, it caused disease regression. The results were published in the journal Nature Communications.

"For the first time, we have demonstrated how a completely non-toxic intervention can effectively treat an aggressive cancer," said Valter Longo, the study senior author and the director of the USC Longevity Institute at the USC Leonard Davis School of Gerontology and professor of biological sciences at the USC Dornsife College of Letters, Arts and Sciences.

"We have taken two treatments that are studied extensively as interventions to delay ageing-- a fasting-mimicking diet and vitamin C -- and combined them as a powerful treatment for cancer," added Longo.

The researchers said that while fasting remains a challenging option for cancer patients, a safer, more feasible option is a low-calorie, plant-based diet that causes cells to respond as if the body were fasting.

Their findings suggest that a low-toxicity treatment of fasting-mimicking diet plus vitamin C has the potential to replace more toxic treatments.

Results of prior research on the cancer-fighting potential of vitamin C have been mixed. Recent studies, though, are beginning to show some efficacy, especially in combination with chemotherapy.

In this new study, the research team wanted to find out whether a fasting-mimicking diet could enhance the high-dose vitamin C tumour-fighting action by creating an environment that would be unsustainable for cancer cells but still safe for normal cells.

"Our first in vitro experiment showed remarkable effects. When used alone, fasting-mimicking diet or vitamin C alone reduced cancer cell growth and caused a minor increase in cancer cell death. But when used together, they had a dramatic effect, killing almost all cancerous cells," said Longo.

Longo and his colleagues detected this strong effect only in cancer cells that had a mutation that is regarded as one of the most challenging targets in cancer research.

These mutations in the KRAS gene signal the body is resisting most cancer-fighting treatments, and they reduce a patient's survival rate. KRAS mutations occur in approximately a quarter of all human cancers and are estimated to occur in up to half of all colorectal cancers.

The study also provided clues about why previous studies of vitamin C as a potential anticancer therapy showed limited efficacy. By itself, a vitamin C treatment appears to trigger the KRAS-mutated cells to protect cancer cells by increasing levels of ferritin, a protein that binds iron.

But by reducing levels of ferritin, the scientists managed to increase vitamin C's toxicity for the cancer cells. Amid this finding, the scientists also discovered that colorectal cancer patients with high levels of the iron-binding protein have a lower chance of survival.

"In this study, we observed how fasting-mimicking diet cycles are able to increase the effect of pharmacological doses of vitamin C against KRAS-mutated cancers," said Maira Di Tano, a study co-author at the IFOM, FIRC Institute of Molecular Oncology in Milan, Italy.

"This occurs through the regulation of the levels of iron and of the molecular mechanisms involved in oxidative stress. The results particularly pointed to a gene that regulates iron levels: heme-oxygenase-1," added Tano.

The research team's prior studies showed that fasting and a fasting-mimicking diet slow cancer's progression and make chemotherapy more effective in tumour cells while protecting normal cells from chemotherapy-associated side effects. The combination enhances the immune system's anti-tumour response in breast cancer and melanoma mouse models.

The scientists believe cancer will eventually be treated with low-toxicity drugs in a manner similar to how antibiotics are used to treat infections that kill particular bacteria, but which can be substituted by other drugs if the first is not effective.

To move toward that goal, they say they needed to first test two hypotheses: that their non-toxic combination interventions would work in mice, and that it would look promising for human clinical trials.

In this new study, they said that they've demonstrated both. At least five clinical trials, including one at USC on breast cancer and prostate cancer patients, are now investigating the effects of the fasting-mimicking diets in combination with different cancer-fighting drugs.

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