Influence of genetics on cannabis dependence in adolescent females

Researchers have identified that a variant in a particular gene, that is found in about one-third of people, increases vulnerability to THC in females. It also has a large-scale impact on brain regions and pathways responsible for processing reward.

The brain's endocannabinoid system regulates the activity of cannabinoids that are normally produced by the body to influence brain development and regulate mood as well as those from external sources, such as the psychoactive ingredient THC, also known as D9-tetrahydrocannabinol, which is found in cannabis.

An enzyme called fatty acid amide hydrolase (FAAH) breaks down a cannabinoid called anandamide that is naturally found in the brain and is most closely related to THC, helping to remove it from circulation.

In the study which was published in 'Science Advances,' the researchers examined mice harbouring a human gene variant that causes FAAH to degrade more easily, increasing overall anandamide levels in the brain.

From the preclinical research by Weill Cornell Medicine investigators, they discovered that the variant resulted in an overactive reward circuit in female--but not male adolescent mice--that resulted in a higher preference for THC in females.

Dr. Caitlin Burgdorf, recent doctoral graduate from the Weill Cornell Graduate School of Medical Sciences, and the lead author said "Our study shows that a variant in the FAAH gene, which is found in about one-third of people, increases vulnerability to THC in females and has large-scale impact on brain regions and pathways responsible for processing reward."

"Our findings suggest that genetics can be a contributing factor for increased susceptibility to cannabis dependence in select populations," Caitlin added.

The result showcased that female mouse with the FAAH variant showed an increased preference for the environment in which they'd been exposed to THC over a neutral environment when they were exposed to the substance during adolescence, and the effect persisted into adulthood. 

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Cancer patients more likely to use marijuana

Many cancer patients use marijuana and its usage has increased, a new study suggests. The findings,  indicate 40.3 per cent cancer patients used marijuana within the past year, compared with 38 per cent of respondents without cancer.

“Prospective clinical trials are needed to quantify the efficacy of marijuana in cancer-specific pain as well as the risk of opioid misuse in this patient population,” said co-author.

For the study, 826 people with cancer were matched to 1,652 controls.

The researchers found significantly increased use of marijuana over time — likely reflecting increased availability due to legislative changes — but they found stable rates of opioid use.

They found patients with cancer were more likely to use prescription opioids than adults without cancer — 13.9 per cent versus 6.4 per cent.

“Medical marijuana legislation has previously been associated with reduction in hospitalisations related to opioid dependence or abuse, suggesting if patients are in fact substituting marijuana for opioid, this may introduce an opportunity for reducing opioid-related morbidity and mortality,” said lead author of the study.

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Scientists Just Found a Super-Powerful New Class of Antibiotics in Dirt

The modern medical era began when an absent-minded British scientist named Alexander Fleming returned from vacation to find that one of the petri dishes he forgot to put away was covered in a bacteria-killing mould. He had discovered penicillin, the world's first antibiotic.

Ninety years later, the world faces an antibiotic crisis.

Superbugs have evolved resistance to dozens of drugs in doctors' arsenals, leading to infections that are increasingly difficult to treat. Global deaths from antibiotic-resistant infections are predicted to hit 10 million a year by 2050.

So in labs around the world, scientists are racing against time to cultivate new microbe-destroying molecules – but most of the low-hanging fruit has already been picked.

With due respect to Fleming, a microbiologist thinks it's time to shift tactics. Instead of growing antibiotics in a petri dish, he hopes to find them in the ground.

"Every place you step, there's 10,000 bacteria, most of which we've never seen," said the researcher, an associate professor.

Many of these bacteria behave in ways that aren't yet understood and produce molecules that we haven't been seen before.

"Our idea is, there's this reservoir of antibiotics out in the environment we haven't accessed yet," the researcher said.

That idea is beginning to pay off: in a study published recently,the researchers report the discovery of a new class of antibiotic extracted from unknown microorganisms living in the soil.

This class, which they call malacidins, kills several superbugs – including the dreaded methicillin-resistant Staphylococcus aureus (MRSA) – without engendering resistance.

You won't find this antibiotic at your pharmacy next week, the researcher cautioned. It takes years for a novel molecule to be developed, tested and approved for distribution.

But its discovery is proof of a powerful principle, he said: a world of potentially useful untapped biodiversity is still waiting to be discovered.

Though antibiotics are prized for their ability to combat the microbes that make humans sick, most of the drugs come from bacteria.

For example, streptomycin, which has been used to treat tuberculosis and plague, is produced by the bacterium Streptomyces griseus. (This microbe was originally found in the dirt of a New Jersey farm field, though the antibiotic research was conducted using cell cultures.)

Bacteria have been fighting one another for billions of years – far, far longer than humans have been around – so it's hardly surprising that they have evolved all the best weapons.

Yet the vast majority of these microbes don't grow well under controlled laboratory conditions, making them difficult to study.

"Maybe, using that simple culture-based approach, we've missed most of the chemistry that are produced by bacteria," the researcher said.

It would be better to derive interesting molecules directly from the environment. And with the advent of metagenomics, techniques that allow all the genetic material in a sample to be sequenced en masse, researchers can do just that.

For this study, the team cloned vast quantities of DNA from hundreds of soil samples contributed by citizen scientists across the country and then sorted through the material in search of interesting sequences.

"Most of what's there is completely unknown, and that's the future," the researcher said.

He and his colleagues were looking specifically for a known gene associated with the production of calcium-dependent antibiotics – molecules that attack bacterial cells, but only when calcium is around.

It's thought that the existence of such an "on-off" switch may make it harder for microbes to evolve resistance.

Because of this, the gene for calcium dependence might serve as a flag for a much longer sequence controlling the production of antibiotics – much the same way that coming across instructions for making crust might flag cookbook readers that they've found a recipe for pie.

Having identified a sequence containing the calcium-dependence gene, the researchers cloned it and injected it into a microbe that can be cultured. Soon enough, those microbes were making malacidins.

When applied to cuts in the skin of MRSA-infected rats, the previously unknown molecule successfully sterilised the wounds. The bacterium didn't show signs of resistance, even after three weeks of exposure.

According to the researcher, malacidins work by interfering with the process that bacteria use to build their cell walls. Human cells rely on a different process, so the antibiotic isn't toxic to people.

He and his colleagues don't know what species the molecules come from, but they don't need to – they already have the genetic blueprint for building it.

"The effort now is to scale it," he said.

Two years ago, the scientist launched a company, which aims to accelerate the discovery process and ultimately produce new medications that can be used to treat disease.

He is not the only scientist with this idea. Researchers elsewhere are using metagenomics to seek out new antibiotics in ocean water and insect guts.

Meanwhile, the same technique has been applied to urban sewage and polluted lakes to reveal the vast extent of antibiotic resistance.

Speaking to the media, the microbiologist noted that searching for the calcium-dependence gene allowed Brady's team to sort through massive amounts of DNA.

"They've used a clever approach to mine for antibiotics," he said.

But a scientist, who was not involved in the research, pointed out that the researchers will need to continue identifying new DNA signatures associated with antibiotics for their technique to keep working: "Now we need to say, 'You guys can do even better.' "

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Alcohol dependency in young adults may have long-lasting effects

A study says that young adults with symptoms of alcohol dependence may see health effects late in life, even decades after conquering their problem drinking.

Researchers found that, of 664 U.S. male veterans, those who had symptoms of alcohol dependence for at least five years in young adulthood generally had poorer physical and mental health by the time they were in their 60s.

And that was true even if they'd gotten control over their drinking problems by the age of 30.

The findings are surprising, said lead researcher Randy Haber.
It's clear that people's lives improve when alcohol dependence goes into remission, Haber pointed out, but it is not clear whether there are hidden consequences that remain after heavy drinking has ceased. For instance, evidence shows that both brain and body are affected by excessive drinking, but we don't know how long these effects last.

The new findings suggest that years of alcohol dependence during young adulthood result in silent but "permanent" injuries that, in later life, appear to result in serious health problems, according to Haber.

The findings are based on men taking part in a larger study of Vietnam-era veterans. Haber's team focused on 368 men who did not report any symptoms of alcohol dependence at any point in adulthood, 221 who had at least three symptoms of dependence in young adulthood, and middle-age and 75 who had symptoms in early adulthood but not after the age of 30. Overall, the study found that men who had alcohol dependence symptoms for at least five years in early adulthood scored lower on standard measures of both physical and mental health once they'd reached their 60s.

For example, those with alcohol dependence in young adulthood had, on average, three medical conditions in later life whereas those without this history reported two.

In addition, their scores on a depression scale were about twice as high. Most important, these effects were seen even among men who'd been free of dependence symptoms for several decades.
The reasons are unclear.

But, Haber said, other studies have shown that chronic drinking may injure parts of the brain involved in emotional regulation, self-control and decision-making. It's possible, he noted, that years of alcohol exposure in early adulthood could have lasting effects on those brain areas.

Still, Haber stressed that this study is reporting "averages" and not what any one person is destined for.

He said that people who not only quit problem drinking but also turn their lifestyle around, eating well, not smoking and just generally "taking care of themselves," will likely see health benefits that last into late life.

Plus, he said, there is a "whole body of literature" showing that when people with alcohol dependence go into recovery, their lives improve in almost every area.

"If you have entered (alcohol dependence) recovery, keep going," Haber said. "Live your life to its fullest."

The study has been published in Journal of Studies on Alcohol & Drugs. (ANI)

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Lead a healthy lifestyle to prevent getting dependent in old age

Another incentive for you to exercise regularly, eat nutritious food and follow a healthy lifestyle: It may not only extend your lifespan, but also cut down the time you may spend as a dependent in old age, claim researchers. 

An analysis of a quarter century of data by scientists at the University of Pittsburgh in the US and colleagues showed that older adults with the healthiest lifestyles could expect to spend about 1.7 fewer years disabled at the end of their lives, compared to their unhealthiest counterparts.

“The duration of the disabled period near the end of one’s life has enormous personal and societal implications, ranging from quality of life to health care costs,” said senior author Anne B Newman.

“We discovered that, fortunately, by improving lifestyle we can postpone both death and disability. In fact, it turns out that we’re compressing that disabled end-of-life period,” said Newman.
Newman and her colleagues examined data collected by the Cardiovascular Health Study, which followed 5,888 adults for 25 years.

All of the participants were aged 65 or older and were not institutionalised or wheelchair-dependent when they enrolled.
The participants reported or were assessed for various lifestyle factors, including smoking habits, alcohol consumption, physical activity, diet, weight and their social support system.

The researchers took into account and adjusted results for such factors as participants’ age, sex, race, education, income, marital status and chronic health conditions.

Across all the participants, the average number of disabled years directly preceding death — years when the person had difficulty eating, bathing, toileting, dressing, getting out of bed or a chair, or walking around the home - averaged 4.5 years for women and 2.9 years for men.

For each gender and race group, those with the healthiest lifestyle (those who were nonsmokers of a healthy weight and diet and getting regular exercise) not only lived longer, but had fewer disabled years at the end of their lives.

For example, a white man in the healthiest lifestyle group could expect to live 4.8 years longer than his counterpart in the unhealthiest group, and at the end of his life, he would likely spend only two of those years disabled, compared to 3.7 years for his unhealthy counterpart.

“This clearly demonstrates the great value of investing in the promotion of a healthy lifestyle and encouraging people to maintain healthy behaviours into old age,” said lead author Mini E Jacob.
The study was published in the Journal of the American Geriatrics Society. 

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Now, diabetic therapy from abdominal fats

Good news for patients suffering from diabetes as IKDRC claims to be the first to discover insulin producing genes in abdominal fat.

Institute of Kidney Diseases & Research Centre (IKDRC) claims to have successfully used stem-cells to bring down dependence of type-I diabetics on insulin.

The institute has claimed to be the first to discover insulin producing cells in abdominal fat and use it in stem-cell therapy to bring down patient’s dependence on insulin. A paper regarding the same was presented by the research team of IKDRC — led by its director Dr HL Trivedi at the 12th International Congress of Cell Transplantation Society at Milan, Italy.

Speaking about the discovery, Dr Trivedi said that the team experimented with fat from the abdomen. 

“We found three genes that were identical to the genes that produce insulin in pancreas. What were the genes doing in the abdominal fat was a question. But more important was that we managed to use them in stem-cell therapy to reduce diabetics dependence on insulin,” said Dr Trivedi. 

He, however, clarified that so far the use of stem-cell has only helped reduced the dependence of diabetics on insulin and not in eliminating it. “In future we may be able to achieve that too,” said Dr Trivedi. 

Associate professor in regenerative medicine and stem-cell therapy Dr Umang Thakkar, who presented the paper on use of stem-cell in type-I diabetes, said 20 patients were taken for the study. 

“Ten of them had stem cells from abdominal fat of a donor while the remaining used cells from their own body fat. The latter group showed better response because your body tends to accept its own cells rather than from a donor. 45% reduction in insulin dependence was registered in the group that used its own body fat while it was 35% for the other group. The mean age of the group was 20 years,” said Dr Thakkar. 

He said another encouraging factor was that in the group that used stem-cells from its own body fat there were no instances of ketoacidosis — a condition common among diabetics in which there is sudden spurt in blood sugar level accompanied by breathlessness. All the patients in the study group were type-I diabetics.

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