Curcumin hope in TB fight

Indian scientists have shown that turmeric’s yellow ingredient may help enhance the efficacy of the lone standard vaccine against tuberculosis, which is given to all children at birth but is effective only for about a decade.

Researchers have carried out studies on mice to demonstrate that curcumin -– a molecule extracted from turmeric – when encapsulated into tiny nano-particles, can increase the efficacy of the bacille Camille-Guerin (BCG) vaccine.

The protective effect of the BCG vaccine diminishes over time and is lost by the time children turn 10 or 12.

Researchers have now shown that curcumin nano-particles can enhance the capacity of the BCG vaccine to stimulate the long-term memory of the immune system.

They found that the efficacy of the BCG vaccine was stronger and lasted longer in immunised mice that had also received curcumin nano-particles for 30 days after receiving the vaccines.

They have published their findings in the research journal Infection and Immunity.

When the immunised mice were challenged by a virulent strain of tuberculosis, delivered through aerosols, the bacterial loads in the lungs and spleen were significantly lower in the mice that had also received the curcumin nano-particles.

The  studies suggest that the addition of curcumin nano-particles activates two types of cells in the immune system, called Th1 and Th17, which play a key role in the long-term protection against tuberculosis infections.

“We need to validate these findings, but if these results are extrapolated to humans, we’re proposing enhancing the efficacy of, and long-term protection with, BCG vaccines,” he said.

Earlier studies had established that curcumin can influence the immune system in animals and humans.

“Our results suggest that nano-curcumin can elongate or stretch the ability of the immune system to recognise the TB bacilli,” said a study team member.

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Young boys can now preserve their testicular tissues

An experimental process of freezing testicular tissue gives hope to young boys to preserve their fertility before beginning medical treatments known to cause infertility, research claimed.

An estimated 2,000 U.S. boys and young men each year receive treatments or have cancers or blood disorders that place them at risk for infertility. While older youths who have undergone puberty can bank their sperm prior to undergoing sterilising doses of chemotherapy or radiation, there have been scant fertility preservation options for younger boys.

However, some older adolescents and young men are too sick or stressed to bank sperm. For patients with no sperm to a bank or who are too sick or stressed to bank sperm, the experimental procedure of freezing testicular tissue in anticipation that future cell- or tissue-based therapies can generate sperm is the only option.

Recent research in experimental models indicates that such testicular tissue biopsies contain stem cells, blank slate cells, hinting at the potential of generating sperm from biopsied tissue.

"This study demonstrates that undifferentiated stem and progenitor spermatogonia may be recovered from the testicular tissues of patients who are in the early stages of their treatment and have not yet received an ablative dose of therapy. The function of these spermatogonia was not tested," wrote lead author.

Right now, haematologists and oncologists discuss future treatment options with patients and families, as well as possible long-term side effects, including infertility.

"This study is unique in that there is definitely a potential direct patient benefit. One of the reasons the study is compelling is that it presents a message of hope to the families. It's a message of survivorship: We are optimistic we can help your child get through this and think about long-term issues, like having their own families," said a Dr.

In this phase of the study, testicular tissue was collected from centres in the U.S. and Israel from January 2011 to November 2018 and cryopreserved.

Patients designated 25 per cent of the tissue sample to be used for the research study; 75 per cent remains stored in liquid nitrogen at temperatures close to absolute zero for the patient's future use. The fertility preservation patients ranged from 5 months old to 34 years old, with an average age of 7.9 years.

Thirty-nine per cent of patients had started medical treatment prior to requesting fertility preservation. 16 per cent received non-alkylating chemotherapy while 23 per cent received alkylating chemotherapy, which directly damages the DNA of cancer cells.

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A new molecule may offer hope for cancer treatment, can lower future risk of the disease

A research team has now discovered that an immune checkpoint molecule they developed for cancer immunotherapy, also protects against future development administered by itself.

Earlier studies have shown that the recombinant protein molecule SA-4-1BBL enhances the therapeutic efficacy of cancer vaccines with success in pre-clinical animal models. It accomplishes this by boosting the effectiveness of CD8+T cells, adaptive immune cells trained to target the tumour for destruction.

Surprisingly, when the researchers treated normal healthy mice with SA-4-1BBL alone, the mice were protected when the researchers later exposed them to different types of tumour cells.
Speaking about it, lead author said, " The novelty we are reporting is the ability of this molecule to generate an immune response that patrols the body for the presence of rare tumour cells and to eliminate cancer before it takes hold in the body.

The author added that generally, the immune system, will need to be exposed to the tumour, recognise the tumour as dangerous, and then generate an adaptive and tumour specific response to eliminate the tumour that it recognizes.

He added that the finding is very surprising because the immune system has not seen a tumour, so the response is not to the presence of a tumour.

According to researcher, the molecule generates a tumour surveillance system through activation of what are known as CD4+ T cells and innate NK cells, thereby protecting the mice against various cancer types they have never had.

This function is an indication of the molecule's effectiveness in cancer immunoprevention.
The study saw mice that had never had cancer being treated with SA-4-1BBL alone. They were then challenged with cervical and lung cancer tumour cells at various time intervals.

The mice showed significant protection against tumour development , with the greatest protection when challenged 2 weeks after treatment with SA-4-1BBL. The cancer immunoprevention effect generated by SA-4-1BBL lasted more than 8 weeks.

Additional testing showed that CD8_ T cells were not required for the protection, but when CD4+ T and NK cells were eliminated in the mice, protection failed, indicating these 2 cell types were necessary to achieve the effect. The lack of necessity for CD8 + T cells indicates the process is not one of conventional acquired immunity.

" We are very excited about the cancer immunoprevention possibilities of this molecule. Its effectiveness is not tumour specific, and as a natural ligand, it does not cause toxicity, as it found with 4-1BB agonist antibodies. Plus, the fear of autoimmunity is highly minimised, as evident from our data, because it is activating the innate immune cells, " said co-author of the study.

They plan to conduct further tests for SA-4-1BBL in cancer immunoprevention.

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A research team has now discovered that an immune checkpoint molecule they developed for cancer immunotherapy, also protects against future development of multiple types of cancer when administered by itself.

Read more at:
//economictimes.indiatimes.com/articleshow/68010027.cms?utm_source=contentofinterest&utm_medium=text&utm_campaign=cppst

A research team has now discovered that an immune checkpoint molecule they developed for cancer immunotherapy, also protects against future development of multiple types of cancer when administered by itself.

The study, conducted at the University of Louisville, was published in the journal Cancer Research.

Earlier studies have shown that the recombinant protein molecule SA-4-1BBL enhances the therapeutic efficacy of cancer vaccines with success in pre-clinical animal models. I ..

Read more at:
//economictimes.indiatimes.com/articleshow/68010027.cms?utm_source=contentofinterest&utm_medium=text&utm_campaign=cppst

A research team has now discovered that an immune checkpoint molecule they developed for cancer immunotherapy, also protects against future development of multiple types of cancer when administered by itself.

The study, conducted at the University of Louisville, was published in the journal Cancer Research.

Earlier studies have shown that the recombinant protein molecule SA-4-1BBL enhances the therapeutic efficacy of cancer vaccines with success in pre-clinical animal models. I ..

Read more at:
//economictimes.indiatimes.com/articleshow/68010027.cms?utm_source=contentofinterest&utm_medium=text&utm_campaign=cppst

Brain blood flow finding gives hope for Alzheimer’s therapy

You know that dizzy feeling you get when, after lying down for an extended period, you stand up a little too quickly?

That feeling is caused by a sudden reduction of blood flow to the brain, a reduction of around 30 percent. Now imagine living every minute of every day with that level of decreased blood flow.
People with Alzheimer’s disease don’t have to imagine it. The existence of cerebral blood flow reduction in Alzheimer’s patients has been known for decades, but the exact correlation to impaired cognitive function is less understood.

“People probably adapt to the decreased blood flow, so that they don’t feel dizzy all of the time, but there’s clear evidence that it impacts cognitive function,” said an associate professor.

A new study, offers an explanation for this dramatic blood flow decrease: white blood cells stuck to the inside of capillaries, the smallest blood vessels in the brain. And while only a small percentage of capillaries experience this blockage, each stalled vessel leads to decreased blood flow in multiple downstream vessels, magnifying the impact on overall brain blood flow.

“It turns out that … the blockages we were trying to induce were already in there,” she said. “It sort of turned the research around – this is a phenomenon that was already happening.”

The researchers, determined that only about 2 percent of brain capillaries had “stalls” (blockages), but the cumulative effect of that small number of stalls was an approximately 20 percent overall decrease in brain blood flow, due to the slowing of downstream vessels by the capillaries that were stalled. Recent studies suggest that brain blood flow deficits are one of the earliest detectable symptoms of dementia.

To test the effect of the stalls on performance of memory tasks in Alzheimer’s mice, they were given an antibody that interfered with the adhesion of white blood cells to capillary walls, which caused the stalled capillaries to start flowing again and thus increased overall brain blood flow. Memory function was improved within a few hours, even in aged mice with more advanced stages of Alzheimer’s disease.

Researchers are quick to point out, however, that the antibody is not something that can be used in humans. Also, of course, interfering with white blood cell adhesion would render an individual immuno-compromised.

“What we’ve done is identify the cellular mechanism that causes reduced brain blood flow in Alzheimer’s disease models, which is neutrophils [white blood cells] sticking in capillaries,” the Dr. said. “We’ve shown that when we block the cellular mechanism [that causes the stalls], we get an improved blood flow, and associated with that improved blood flow is immediate restoration of cognitive performance of spatial- and working-memory tasks.”

“Now that we know the cellular mechanism,” he said, “it’s a much narrower path to identify the drug or the therapeutic approach to treat it.”

The team has identified approximately 20 drugs, many of them already FDA approved for human use, that have potential in dementia therapy. Some of them, however, were designed to be taken in high doses for short periods of time to treat sepsis, or in the immediate aftermath of a heart attack or stroke. “They weren’t really intended to be something that you take for the rest of your life,” he said. Nonetheless, the lab is screening these drugs in Alzheimer’s mice now. 

The Dr. said he’s “super-optimistic” that, if the same capillary-blocking mechanism is at play in humans as it is in mice, this line of research “could be a complete game-changer for people with Alzheimer’s disease.”

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No finger pricks – New breath analyser to monitor blood sugar

New hope for people with diabetes. Scientists have developed a new technology wherein a simple puff into a handheld device will be able to monitor blood sugar. The device will not only be painless, but also reusable- no finger pricks or expensive test strips.

The sensor device will work like a breath-analyzer, but rather than measuring alcohol, the sensor measures acetone to determine an individual's blood glucose level, according to the lead researcher.
" Acetone is a bio-marker for blood glucose level," explained a researcher.

Researchers began developing the sensor in 2015 through a  two-year grant .

To make the biosensor, the researchers used a technique called molecular imprinting to deposit a polymer layer onto graphene. " The 3D polymer has small cavities that are the same shape and size as acetone molecules," he said. " It works like a filter, allowing only acetone to get through and bind to the graphene".

" Human exhales breath contains more than 3,000 volatile organic compounds resulting from the body's metabolic pathways," he explained. " The sensor detects only acetone and ignores the others. The selectivity is very high".

When the acetone molecules attach to the graphene, it changes the material's electrical properties. " The amount of resistance in the graphene sensing layer changes based on the amount of acetone gas," he said. To test the sensor, he placed it in a chamber into which acetone gas was introduced for 3 seconds.

The sensor detects acetone levels ranging from 0.9 ppm to 10ppm. " The acetone concentrations in the breath of a non-diabetic range from 0.3 to 0.9 parts per million, however, in diabetes, those levels are higher," he explained. Additional electronic components will then convert the measurement to milligrams per deciliter, the standard blood glucometer reading.

Next, he will optimize the sensor's recovery time- how ling the user must wait before taking another reading. " My goal is to make it less than one minute", he said.

Once preliminary evaluations have been completed, the researchers will integrate the sensor into a prototype device that can be tested using human breath.

Researcher in-charge for commercialising project, envisions putting the breath sensor into a smartphone along with an app that enables users to effectively monitor and manage their blood glucose levels. " This new technology promises to be revolutionary".

" If we succeed, it's going to be ' wow'", he said. " This will make life easier for everyone with diabetes".

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Read more at Speciality Medical Dialogues: No finger pricks – New breath analyser to monitor blood sugar https://speciality.medicaldialogues.in/no-finger-pricks-new-breath-analyser-to-monitor-blood-sugar/

Read more at Speciality Medical Dialogues: No finger pricks – New breath analyser to monitor blood sugar https://speciality.medicaldialogues.in/no-finger-pricks-new-breath-analyser-to-monitor-blood-sugar/

Read more at Speciality Medical Dialogues: No finger pricks – New breath analyser to monitor blood sugar https://speciality.medicaldialogues.in/no-finger-pricks-new-breath-analyser-to-monitor-blood-sugar/

New experimental vaccine offers hope against malaria

An experimental new malaria vaccine is offering potentially long-lasting immunity against the persistent parasite that sickens hundreds of millions of people each year, a study suggests. Most vaccines are designed to encourage the human body to respond to invading, disease-causing pathogens by creating antibodies that disable those pathogens. 

However, the new vaccine takes a different approach by using a weakened form of a common herpes virus - cytomegalovirus, or CMV - that infects most people without causing the disease.

This new vaccine reduced the malaria-causing parasite's release from the liver and into the blood of infected rhesus macaques by 75 to 80 per cent, reported the paper published recently.

"The problem with most vaccines is that their effectiveness is often short-lived," said lead author of the study. 

"Our cytomegalovirus-based vaccine platform can create and keep immunity for life. With further research and development, it could offer a lifetime of protection against malaria," he added. 

Malaria is a serious and sometimes fatal disease caused by Plasmodium parasites, which are spread to humans through mosquito bites. 

It can cause high fevers, shaking chills, flu-like illness and, in the worst cases, death.  Worldwide, 216 million people were infected with malaria in 2016, leading to 445,000 deaths. 

The researchers weaved tiny bits of their target pathogen into CMV, which is already being used in vaccines being developed to battle HIV and tuberculosis.  Those who receive the resulting, re-engineered CMV vaccine produce memory T-cells that can search for and destroy pathogen-infected cells. 

The team developed two different versions of their CMV-based malaria vaccine while using four different proteins made by the Plasmodium parasite. 

The resulting vaccines delayed the parasite's appearance in the blood of 16 infected and vaccinated rhesus macaques by eliminating between 75 and 80 per cent of parasites from the liver. 

A year later, the vaccinated non-human primates still had immunity against malaria, while eight control animals that were not vaccinated did not. 

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The first cry of joy

An early September night in 2014, together with the rest of the team behind the Swedish uterus transplant trial, the Dr. prepared for a landmark delivery. The birth of a baby that would transform both the fields of reproductive and transplantation medicine. This was the groundbreaking finale—a culmination of a ten-year journey and preparatory work in different animal models.

The mother-to-be had, a year and a half earlier, received a donated uterus from a family friend. A friend who, at the time of the uterus donation, had been postmenopausal for ten years. The mother-to-be was born without a uterus because of a condition called Mayer-Rokitansky-Küster-Hauser (MRKH) syndrome. As a teenager, she was told by her doctors that she would never be able to carry her own pregnancy and give birth to a child.

That September night we were to prove this previous statement wrong. Her pregnancy had been without any complications until she developed signs of preeclampsia in the 31st week of pregnancy. As this was the first successful pregnancy, the team didn’t dare to wait, and we decided to deliver the baby boy prematurely. It was completely silent in the operating room until the most beautiful cry filled the room. There was awe, relief and joy. We knew at that time that we created hope for millions of women in the world affected by uterine factor infertility, a new hope to be able to give birth.

Since that first birth in 2014, at least 12 more babies around the world have been born to mothers following uterine transplantation. I have been fortunate to be the only doctor in the world to be involved with not only the first uterus transplant centre that delivered a baby, but also the second one. At another medical centre, the team was successful in replicating the successes of my former Swedish team when we, in 2017, delivered the first baby after uterus transplant in the US and outside of the Swedish trial.

To work as a uterus transplant surgeon means facing novel medical and surgical questions. It means balancing a field that is an intersect between transplantation, gynaecology, reproductive medicine, pathology, radiology and new ethical challenges. Since the onset of the first uterus transplant trial, the discussions in the medical community have morphed from questioning the need for uterus transplantation and its possibility to improving the procedure and outcome, and finally to discussions of financing, organ allocation and clinical implications. Always keeping the Hippocratic oath close to heart and remembering that 'Primum non nocere' (first, to do no harm) in this procedure is applicable to both donor and recipient.

A uterus transplantation is not a lifesaving or even life-prolonging procedure. Nonetheless, by restoring a bodily function lost or missing, it is instead a thoroughly life promoting procedure—creating life where none could grow before.

I believe that this truly beautiful procedure will now bring joy in India for many mothers-to-be, and I congratulate the team for their achievement.

ps- as told by the Dr. who was involved in both the 1st and the 2nd uterus transplant successfully and delivery of the baby.

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