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Anaesthesia Can Make Nerves Grow The Wrong Way in Unborn Rats

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main article imageEvery year in the US, up to 75,000 pregnant women undergo surgery under anaesthesia. How that affects the foetus is unclear – but new research has pinpointed a worrying possibility

In a study on pregnant rats, a team of researchers found that anaesthesia seems to disrupt the migration of neurons in the foetus’ brain, preventing them from arriving at their destinations in the cerebral cortex.

“The cerebral cortex, or grey matter, is the brain’s computer processor,” explained neuroscientist Vicko Gluncic of Rush University.

“Cognitive processes like thinking, memory, and language are directed there, thus neurons never reaching their proper and predetermined positions in the cortex may have a profound impact on brain function.”

Previous studies had shown a strong correlation between prenatal or early-life exposure to anaesthetics and learning disabilities in humans, and behavioural abnormalities in animals, so Gluncic and colleagues sought to investigate why.

They injected 22 pregnant rats with a dye to tag the foetus’ neurons, then anaesthetised them at the 16th or 17th day of gestation.

This a late stage of pregnancy for the rats, roughly equivalent to late in the second trimester for humans. It’s also when the neuronal migration – when neurons move from their original position deep inside the brain to the outer region, or cerebral cortex – is at its most active.

A control group of rats was not anaesthetised, so the researchers could observe the differences in neuronal migration.

In the foetuses of the anaesthetised rats, a significant number of neurons remained scattered in the deeper levels of the cortex, instead of making it all the way out to the final position.

The longer the rats were anaesthetised, the more pronounced the scattering was. The control group did not have this scattering.

Then, after the baby rats were born, the researchers conducted behavioural studies. They found that the pups of anaesthetised mother rats had significant learning and cognitive deficits, compared to the control pups.

“There is a clear association of anaesthesia type and anaesthetic duration with neuronal migration and cognitive deficits at the drug levels used here (in rat fetuses),” said Rush University biostatistician Mario Moric.

“What is needed now is to further validate the mechanisms involved as well as test various anaesthetics and anaesthetic protocols to evaluate differential impact on cognitive functioning.”

Although there is a clear association in rats, that doesn’t necessarily mean the effect is exactly the same in humans, since animal models are not always predictive for human responses.

But the research does create a precedent that shows a need for further investigation into the effects of anaesthesia on the developing human foetus.

It also indicates that perhaps care should be taken when choosing the best time for a pregnant woman to undergo surgery.

Typically, non-urgent surgeries in pregnant women are performed in the second trimester, because that’s after the foetus’ organs have formed, and less likely to trigger contractions and miscarriage than the third trimester.

Obviously emergencies can’t be helped, but maybe, according to this new research, this approach needs to be reconsidered for non-emergency surgery.

“Based upon the present data,” Gluncic said, “the possibility that anaesthesia may affect fetal brain development should be seriously considered and disclosed in informed consent for anaesthesia in the second trimester since the most active period of human fetal brain development actually occurs between 12th and 24th week of pregnancy.”

The research has been published in Cerebral Cortex.

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IPC asks healthcare professionals & institutions to monitor ADRs as PvPI sounds alert on dabigartan and sertraline

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The Indian Pharmacopoeia Commission (IPC) which is the National Coordination Centre (NCC) for Pharmacovigilance Programme of India (PvPI) has directed healthcare professionals and institutions across the country to report adverse events associated with two suspected drugs – dabigartan and sertraline.

As per the alert from the PvPI, the preliminary analysis of ADRs from the PvPI database reveals that these drugs – Dabigartan and Sertraline– are associated with risks like alopecia and maculopathy respectively. While alopecia areata is a common autoimmune disorder that often results in unpredictable hair loss, maculopathy is damage to the macula, the part of the eye which provides us with our central vision.

The ADRs can be reported in the format available at its website http// circulated as Suspected Adverse Drug Reactions (ADRs) Reporting Form or by PvPI helpline number – 1800-180-3024.

While dabigartan is recommended for prevention of stroke, systemic embolism and reduction of vascular mortality in adult patients with atrial fibrillation, sertraline is associated with major depressive disorders, obsessive compulsion disorders (OCD) and panic disorders.

Healthcare professionals, patients and consumers have been advised to closely monitor the possibility of ADRs associated with the use of these suspected drugs as specified in the alert. If such reactions are encountered, it needs to be reported to the NCC-PvPI for suitable action.

This comes at a time when the Union health ministry is keen on developing a system of intensive ADR monitoring to come out with concrete clinical evidence based on specific serious adverse events associated with specific approved drugs with a case in point like diabetic drug -pioglitazone.

“With the ever increasing thrust on patient safety and the evolving PV practices in the country, we are planning to strengthen the PvPI by identifying new institutions to develop them as competent AMCs and assign them to do intensive ADR monitoring besides the 250 ADR monitoring centres (AMCs) existing in the country,” according to IPC Scientific Director Dr G N Singh. There is a need to generate awareness in medical institutions to put in place effective surveillance system for detection of ADRs, he added.

CDSCO under the Union health ministry had initiated a nation-wide PvPI in July 2010. Since then, IPC which is NCC-PvPI has been mandated to establish clinical evidence between the drug and the ADR event through a robust system of causality assessment. CDSCO in collaboration with IPC has been co-ordinating with healthcare institutions through assessment on aspects like SOPs and causality assessment to strengthen AMCs in the country.

IPC has also set a mandate to set up a total of 300 ADR monitoring centres (AMCs) by 2020 with focus on North Eastern (NE) states. There are currently 250 functioning ADR monitoring centres in the country (in medical colleges and corporate hospitals) as part of the PvPI.

The health ministry had in the past mandated based on the ADR monitoring protocol effective implementation of the projects related to Intensive adverse drug reaction monitoring with help from competent institutions in the country.

Based on the learnings of these projects, government will be equipped in taking regulatory decisions in a timely manner. The exercise has been initiated keeping in view the fact that data from spontaneous reporting of ADRs have generally been mis-spelt.

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MDMA Might Be Able to “Reopen” a Part of The Brain That Closes After Puberty

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In the developing brain, there’s a critical period of time when adolescents learn how to socialize.

This critical period happens right around the point of sexual maturity in mice, according to research published Wednesday in the journal Nature.

But the scientists also found that they could re-open that window by giving adult mice a single dose of the drug MDMA — a finding that could point to new treatments for humans.

After giving mice a dose of MDMA, the scientists found increased levels of oxytocin in the rodents’ brains, along with the uptick in social behaviors — suggesting that brains are more flexible than scientists previously thought.

“This suggests that we’ve reopened a critical period in mice, giving them the ability to learn social reward behaviors at a time when they are less inclined to engage in these behaviors,” Johns Hopkins scientist Gül Dölen told Newsweek.

Right now, doctors are investigating MDMA as a potential treatment for post-traumatic stress disorder, as past studies have found that the drug, along with psychotherapy, has helped some people.

Now, if this mouse study holds up in the human brain, scientists might know why.

“As we develop new therapies or determine when to give these therapies, it’s critical to know the biological mechanism on which they act,” Dölen said.

This article was originally published by Futurism. Read the original article.

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CCMB researchers find new enzymes that could help in dealing with antibiotic resistance bacterial & develop new class of antibiotics

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A team of researchers from Hyderabad-based Centre for Cellular and Molecular Biology (CCMB) has discovered a new enzyme that plays a vital role in the synthesis of bacterial cell wall, which could further help in effectively dealing with the antimicrobial resistance and could bring a promising solution to deal with bacteria which are exhibiting resistance to antibiotics.

It is already known that excessive use of antibiotic has led to the evolution of new disease causing and more powerful bacteria, which are resisting to even toughest of the tough antibiotics and medicines. To counter this and to bring a lasting solution to deal with AMR bacteria, the CCMB researchers have discovered the new enzyme which would help in inhibiting the growth of bacteria and could also help in developing more effective medicines to deal with superbugs and bard to kill disease causing bacteria.

According to Dr. Rakesh Mishra, director of CCMB, this finding is crucial for antimicrobial resistance as it could potentially help in the development of new class of antibiotics.

Explaining further about the development, the CCMB director termed the new discovery as novel and path breaking as the newly found enzyme is effective in the synthesis of bacterial cell wall.

The researchers explained that the cell wall is fundamental for bacterial growth and to understand about the growth of cell wall of bugs and bacteria resisting the antibiotics, the team of researchers launched a detailed research 10 years ago and could find that a new enzyme that helped in the synthesis of cell wall of E.coli bacteria. “This new discovery has the potential to develop a new class of antibiotics for addressing the challenge of antibiotic resistance bacteria,” said Dr. Manjula Reddy, a senior researcher of CCMB.

As part of their research the CCMB scientists have figured out a pathway by which bacterial cell wall synthesis can be prevented through the enzymes. “If we can inhibit the enzymes by using antibiotics, the cell wall synthesis will stop and the bacteria will not grow,” said the CCMB Director.

The research was a collaborative effort of Manjula Reddy and PhD scholar CH. Pavan Kumar. The findings have the potential for collaborations between CCMB and drug manufacturing industry to develop molecules and drugs to tackle bacteria-borne diseases.

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The First Living Person With HIV Has Successfully Provided a Kidney For Transplant

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Surgeons at Johns Hopkins Hospital have transplanted a kidney from a living HIV-positive donor to an HIV-positive recipient, a medical breakthrough they hope will expand the pool of available organs and help change perceptions of HIV.

The donor, 35-year-old Nina Martinez, and the recipient, who chose to remain anonymous, are recovering in the hospital after Monday’s surgery, doctors said. The recipient no longer needs kidney dialysis for the first time in a year.

The procedure is another step in the evolution of HIV — considered to mean certain death when the AIDS epidemic began in 1981 — and an advance for the 1.1 million people who carry the virus. Medication today can suppress the infection to undetectable levels in many people, and President Trump recently vowed to end transmission of it in the United States by 2030. But stigma still remains.

“Society perceives me, and people like me, as people who bring death,” Martinez said in an interview Saturday before the operation. “And I can’t figure out any better way to show that people like me can bring life.”

Martinez, who acquired HIV from a blood transfusion as an infant, appeared at a Hopkins news conference Thursday to announce the surgery, the first of its kind. She said she feels well and is looking forward to training to run in this October’s Marine Corps Marathon in Washington.

“People with HIV today can’t donate blood, but now they’re able to donate a kidney,” said Dorry Segev, a professor of surgery at the Johns Hopkins University School of Medicine, who led the research team and removed Martinez’s left kidney. “They have a disease that 30 years ago was a death sentence. Today, they’re so healthy they can give someone else life.”

Surgeons have transplanted 116 organs from deceased HIV-positive donors to recipients with HIV since 2016, when a new law allowing that surgery took effect. Among people without HIV, more than 152,000 kidneys from living donors have been transplanted over the past 30 years, and a few hundred livers from live donors are implanted each year.

More than 113,000 people are on the U.S. waiting list for organ transplants, most of them seeking kidneys. Others are too sick to be listed, or are taken off the list when their disease progresses too far.

Until now, leaving an HIV-positive person with just one kidney was considered too dangerous because the infection and the medications that control it increase the chances of kidney disease.

But a 2017 study of 42,000 people led by Hopkins researchers showed that for some healthy HIV-positive donors, the risk of developing serious kidney disease is not much greater than it is for many HIV-negative people, especially those who engage in behaviors such as smoking.

Martinez’s organ was implanted in the recipient by a separate team of surgeons, the normal procedure in transplantation. The operation was performed by Niraj Desai, an assistant professor of surgery at Hopkins.

The kidney was implanted near the recipient’s pelvis through a six- to eight-inch incision in the abdomen, and the recipient’s kidneys were not removed, as is common practice, Desai said. Kidney recipients can expect 20 to 40 years from a transplanted kidney, Segev said, with those who receive live kidney donations doing a little better than those who get the organs from deceased donors. After that period, the recipient would require another transplant or go back on dialysis, he said.

Martinez and the recipient will remain on antiretroviral medication indefinitely to control their HIV. Because they may have different strains of the virus and different resistance to HIV medication, doctors must monitor the recipient closely in the months after the donor organ is introduced. The recipient will also take drugs to prevent organ rejection. Those are not expected to significantly interfere with the HIV-suppressing medications.

Martinez is in near-normal physical health. Her viral load is undetectable. “Her health is excellent. Her HIV is well-controlled. Her immune system is essentially normal,” said Christine Durand, an associate professor of medicine at Hopkins and a member of the team that evaluated Martinez.

In 1983, Martinez and her twin sister were born 12 weeks prematurely in San Jose and soon developed anemia. The daughter of a naval officer, Martinez was taken to a military hospital in San Francisco for a blood transfusion in the days before the supply was tested for HIV, and she acquired the infection. She and her family were not aware of it until she was checked before eye surgery at the age of 8.

She was watched in school to ensure she wasn’t a health hazard to other children, she said. She later learned that one principal asked, “Why are we educating her with public dollars if she’s going to die?”

When a housemate found out she had HIV, he moved out, leaving his belongings behind.

“It gives me great joy to know that I’m putting a story like this out there,” she said. “Because those people need a mental reboot.”

A public health consultant who lives in Atlanta, Martinez was aware of the HIV Organ Policy Equity Act, the law allowing the surgery, when it was passed in 2013. The next year, she saw an episode of the television show “Grey’s Anatomy” in which the writers invented a story about a transplant from a live, HIV-positive donor.

When an HIV-positive friend needed a kidney, Martinez grew more serious about the idea and contacted Hopkins to volunteer for the grueling test regimen that enabled her to become the first donor in its clinical trial. But Martinez’s friend died before she could donate to him.

She believes her choice will ripple down the transplant waiting list.

“When I take this recipient off the list, everyone moves up,” she said, “whether they have HIV or not.”

2019 © The Washington Post

This article was originally published by The Washington Post.

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