Day: March 15, 2022

Categories : Diseases, Syndromes and Conditions VaccinesTags :

Boosting the BCG Vaccine by Blocking IL-10

On By ModernMedia
Vaccine injection
Image source: NCI on Unsplash

Briefly blocking interleukin-10 (IL-10) when administering the BCG vaccine for tuberculosis vastly improves long-term protection in mice, researchers reported in the Journal of Immunology. The finding, if it continues to hold true in nonhuman primates and clinical trials, has the potential to save millions of lives.

“We are very excited that we can reverse BCG’s waning effectiveness by combining it with a host-directed therapy into one dose, which makes it very practical for the clinic,” said senior author Joanne Turner, PhD.

The study builds on research showing the effect of IL-10 on TB, which normally helps dampen excessive inflammation during infection, but Dr Turner’s previous work showed that IL-10 overall actually drives infection.

The researchers combined the BCG vaccine with an antibody that blocks IL-10 activity for about one week. Since the antibody targets the host, not the pathogen, that makes it a “host-directed therapy.” They gave the mixture to mice in one shot, waited six weeks to ensure the IL-10 blocker was no longer present and the BCG protection had been generated, and then exposed the mice to TB. Those mice controlled TB infection for nearly a year, which is significant for mice with normal lifespans of about two years. In contrast, mice given only the BCG vaccine lost control of TB infection within two months and had significant inflammation and damage in the lungs. Notably, the mice given the vaccine/IL-10 blocker had higher levels of various long-term memory immune cells, which are critical for ongoing TB control.

“This shows that the early development of an immune response is key for controlling TB infection in the long run, and that IL-10 inhibits the development of that long-term immunity,” Dr Turner said. “But by briefly blocking IL-10 at the same time as giving the vaccine, it allows the vaccine and immune system to do their jobs, creating those long-lasting memory immune cells.”

The researchers plan to move to nonhuman primates and then human clinical trials if those are successful. The team is optimistic, especially since the BCG vaccine is already in widespread use and the IL-10 blocker is being tested against other diseases.

Source: Texas Biomedical Research Institute

Categories : COVID Medical IndustryTags :

Life Insurance Premium Hike on the Cards for the Unvaccinated

On By ModernMedia
Coffin in hearse at a funeral
Photo by adrianna geo on Unsplash

After a staggering increase of R24.9 billion in claims from COVID, South African life insurers are faced with little option but to implement a premium hike on policies for the unvaccinated. Death rates among unvaccinated people could remain elevated even as the pandemic eases, despite the lower severity of Omicron.

The Association for Savings and Investment SA (Asisa) provided death claims data from 1 April 2021 to 30 September 2021, a period which covered the third COVID wave (May to September). Compared to the same pre-pandemic period in 2019, there was a 53% surge in claims was reported, with a more than doubling of value of death claims. There were 565 522 claims, totalling R44.42 billion, compared to the pre-pandemic period’s 369 892 claims of R19.53 billion.

Though deaths were greatly reduced in the fourth wave, with Asisa acknowledging “anecdotal evidence” showing reduced severity from the Omicron variant, there was still “overwhelming evidence” that COVID mortality risks are far higher for the unvaccinated. Asisa’s data reflects that of the South African Medical Research Council (SAMRC), which shows a huge increase in the number of excess deaths over that period.

This information comes as the government debates easing lockdown measures even as various institutions warn of an impending fifth wave, which according to Absa bank could come as early as next month. However, Absa noted that its life claims were much reduced over the fourth wave as compared to the third, and therefore expects the fifth wave to be less severe.

Hennie de Villiers, the deputy chair of Asisa’s life and risk board committee, said that the importance of life insurance cover had been clearly demonstrated. “The reality is that most of us know at least one person who lost his or her life due to COVID. We also know of many more people who lost their income during the pandemic, highlighting the importance of having access to savings.”

He cautioned that, “While the death rate has been lower during the fourth wave than in previous waves due to vaccinations and the emergence of the Omicron variant, death claims rates have not yet returned to pre-pandemic levels. Also, less than 50% of our adult population has been vaccinated.

“There is overwhelming evidence that the risk of severe illness or death is significantly lower in those who are fully vaccinated.”

He added in a later statement that if the situation does not change and vaccinations are not embraced by the country, insurers may have “little choice but to adjust premiums in line with the higher risk presented by someone who is not vaccinated and therefore more likely to die from COVID”.

De Villiers said a “staggering” 1.59-million death claims were received in the 18 months from 1 April 2020 to 30 September, with life insurers paying out benefits of R92 billion.

Group life insurance premiums have already increased for the unvaccinated, De Villiers pointed out. Employers with mandatory vaccination policies are meanwhile benefitting from preferential rates.

When unvaccinated status is combined with age and comorbidities, premium increases, this resulted in premium increases of as much as 100% and in some cases coverage was even declined.

Source: Business Live

Categories : Injury & TraumaTags :

Platelets Get to Work Right Away on Wound Sites

On By ModernMedia
Scanning electron microscope image of red blood cells, platelets (green) and T cells (orange). . Image courtesy of Dennis Kunkel, Dennis Kunkel Microscopy, Inc. Part of the exhibit Life:Magnified by ASCB and NIGMS.

New research shows that platelets at a wound site can sense where they are within a blood clot they are and that they can remodel their surroundings accordingly.

Platelets are key to initiating wound healing and the formation of blood clots (thrombus). Fibroblasts are connective tissue cells that are essential for the later stages of wound healing. Fibroblasts invade the clot that has been formed and produce vital proteins, including fibronectin, that then form a structural framework to build the new tissue needed to heal.

This new study, published in Science Advances, indicates that platelets can also form a provisional fibronectin matrix in their surroundings, similar to what fibroblasts do in the later stages of wound healing. This has potential implications for how the integrity of blood clots might be maintained during vascular repair.

Commenting on the discovery, lead author Dr Ingmar Schoen said: “We have identified an additional unexpected role for the most prominent platelet adhesion receptor. Our results show that platelets not only form the clot but also can initiate its remodelling by erecting a fibrous scaffold. This finding challenges some existing paradigms in the field of wound healing, which is dominated by research on fibroblasts.”

The researchers made use of super-resolution microscopy, a powerful imaging technique which enables much finer resolution of structures inside or around cells in vitro. To develop this finding further, in vivo observation of this platelet behaviour will be necessary.

“Without super-resolution microscopy, this discovery would not have been possible,” Dr Schoen noted.

Source: RCSI University

Categories : Metabolic DisordersTags :

Stem Cells Research Hints at Ways to Prevent Diabetic Retinopathy

On By ModernMedia
Old man with magnifying glass
Image by Mar Lezhava on Unsplash

Researchers are investigating novel stem cell approaches that could lead to treatments for early retinal vascular dysfunction in diabetic patients, which could help prevent diabetic retinopathy.

Diabetic complications cause major metabolic disturbances that damage the cardiovascular, visual, peripheral nerve and renal systems through harming small and large microvessels that feed these tissues. New treatments are needed to treat the growing number of people who develop such retinal vascular dysfunction.

Research strategies include identifying and using new methods to differentiate or mature human induced pluripotent stem cells (hiPSCs) into the specific mesoderm subset of cells that display vascular reparative properties.

“Vascular diseases afflict hundreds of millions of people in the world,” said Chang-Hyun Gil, MS, PhD, a postdoctoral fellow in the Department of Surgery and co-first author of the study. “In this study, we focused on the retinal vessel in type 2 diabetes. Our results demonstrate the safe, efficient and robust derivation of hiPSC-derived specific mesoderm subset for use as a novel therapy to rescue ischemic tissues and repair blood vessels in individuals with vascular diseases. The results provide a foundation for an early phase clinical trial.”

In the study, published in Science Advances, investigators genetically reprogrammed diabetic and non-diabetic peripheral blood cells into hiPSCs and matured the cells into special blood vessel reparative cells. Upon injection into animal models with type 2 diabetic murine (T2D) retinal dysfunction, results showed significant improvement in visual acuity and electroretinograms with restoration of vascular perfusion. They hypothesised that hiPSC-derived vascular reparative cells could work as endothelial precursors that will display in vivo vessel reparative properties in these diabetic subjects.

“Unlike the use of embryonic stem cells (ESCs), genetically engineered hiPSCs do not carry the ethical challenges ESCs possess that limit their possible usage, and hiPSCs are being increasingly recognised as a viable alternative in study design and application as a cell therapy for human disorders,” Dr Gil said.

Researchers converted hiPSC into a specific mesoderm subset that was enriched to generate endothelial cells with vessel reparative properties similar to endothelial colony forming cells (ECFC).

Dr Gil said certain mesoderm subsets were better able to differentiate into ECFC and form functional blood vessels in vivo. and that mesoderm populations corrected vasodegeneration of injured retinal vessels. Tests showed enhanced function of neural retina and improved vision.

Source: Indiana University

Categories : Diseases, Syndromes and ConditionsTags :

Malaria’s Growing Resistance Requires New Insight

On By ModernMedia
Mosquito, a malaria parasite vector
Photo by Егор Камелев on Unsplash

To deal with malaria’s growing resistance to existing drugs, researchers are exploring new areas of the deadly parasite’s life cycle. Research published in PLOS Pathogens has identified key processes the malaria parasite uses to remodel blood cells it hides inside.

Senior author Paul Gilson, an associate professor at Burney University, said the growing resistance to antimalarial medicines needs to be addressed soon to avoid serious treatment failures in the future.

“It’s only a matter of time before resistance becomes so bad that current measures perhaps become worthless,” he said.

“Current drugs tend to target very similar things. By discovering new targets and developing drugs to these, we can hopefully overcome resistance.

“Our research identifies processes in the parasites that are essential for its survival. And the more we understand about those processes, the better position we’re in to develop new treatments to block those processes.”

The research, A/Prof Gilson explains, looked into the nature of malaria parasites, particularly their need to renovate their host blood cells to grow rapidly and to escape the immune system.

The dynamic is analogous to an international arrivals terminal in need of better security.

“The renovations are carried out by special exported proteins made by the parasite that are only allowed to travel into the blood cell if they have the right passport,” he said.

“We used to think that gateways around the parasite called PTEX acted like immigration officers at the airport only allowing exported proteins with the right passports to pass through.

“What this study now shows is that the immigration officers appear to leave the airport and travel inside the parasites to check the exported protein passports not long after they are first made.

“The officers then pair up with their exported proteins and take them to the airport to let them go straight through into the blood cells.”

A/Prof Gilson said that hopefully, a greater understanding of the ways parasite proteins enter and modify blood cells could result in new drugs that block exported proteins from carrying out essential renovations to their blood cells.

The COVID pandemic has disrupted and set back malaria elimination programs in several countries, making the need for new drug developments to combat the disease all the more vital.

“Many countries only have very limited resources, and it’s estimated that there’s been quite a big increase in the number of malaria cases around the world because so much effort has been diverted to combat COVID,” he said.

Even though COVID has taken the global spotlight, A/Prof Gilson said that malaria is still a major issue. In 2020 there were an estimated 241 million cases of malaria worldwide, with an estimated 627 000 deaths, according to World Health Organization figures.

A/Prof Gilson said that over recent years significant inroads have been made in eliminating malaria, pointing out that annual death rates were in the millions at the start of the 21st century.

“We can’t let COVID undermine all the great work that’s been achieved over the years, as we aim to one day totally eliminate malaria.”

“Research into new drugs to combat malaria parasites, which are becoming resistant to existing drugs, is a crucial part of these efforts.”

Source: Burnet Institute