Day: May 28, 2021

Categories : Environmental EffectsTags :

How Air Pollution Causes Loss of Smell

On By ModernMedia
Photo by Kouji Tsuru on Unsplash

Johns Hopkins Medicine researchers have studied how long-term exposure to air pollution causes loss of smell, or anosmia, to better understand how it can rob someone of the ability to smell and taste.

Anosmia can severely impact a person’s quality of life, making it extremely difficult to taste foods, detect airborne hazards in the environment, and other functions. People with anosmia may experience weight concerns, decreased social interaction, depression and general anxiety. Loss of smell has been linked in some cases to death in older adults. 

“We included participants from a variety of areas in our study; however, most lived in urban areas where pollution levels are highest,” says lead author Murugappan “Murray” Ramanathan, MD, rhinologist and associate professor of otolaryngology–head and neck surgery at the Johns Hopkins University School of Medicine. “We wanted to assess how their exposure to PM2.5 air pollution—inhalable, particulate matter less than 2.5 micrometers in size or about 30 times smaller than the diameter of a human hair—might cause them to lose their sense of smell.”

According to the US Environmental Protection Agency (EPA), PM2.5 (the PM stands for ‘particulate matter’) is the term for a mixture of solid particles and liquid droplets found in the air, and are smaller even than pollen grains. PM2.5 can be made of many materials depending on the location, such as dust, dirt, soot, smoke, organic compounds and metals. These particulated have been linked to cardiovascular disease, lung cancer, cognitive decline, chronic obstructive pulmonary disease, asthma and premature death. Previous studies have suggested PM2.5 is a likely culprit in loss of smell—a connection that Prof Ramanathan and his team decided to explore in greater detail.

In their study, the researchers examined data for 2690 people, aged 18 years and older, who were evaluated by otolaryngologists between January 2013 and December 2016. Of these, 538 were diagnosed with anosmia, with an average age of 54, the majority being men (63%).

The EPA’s Air Quality System provided air pollution data for the study. The researchers entered the data into a detailed computer simulation to estimate the PM2.5 pollution levels within the participants’ residential ZIP codes. The model was created by Zhenyu Zhang, a Johns Hopkins Medicine otolaryngology postdoctoral fellow.

The researchers found that long-term airborne exposure to PM2.5 nearly doubles (a 1.6- to 1.7-fold increase) the risk of losing one’s ability to smell. They believe this may occur due to the location of the olfactory nerve—which contains the sensory nerve fibres associated with the sense of smell—being directly in the path of inhaled PM2.5 materials.

“Based on this result, we feel that long-term exposure to high levels of PM2.5 represents a common risk factor for the loss of sense of smell, especially in vulnerable populations such as older people—but also one that is potentially modifiable if sources of PM2.5 components can be better controlled,” says Ramanathan.

The researchers next steps are to study anosmia patients’ socioeconomic factors to find out if they affect the chances of exposure to PM2.5 air pollution. They also hope to evaluate other air pollution components that may contribute to loss of smell, such as ozone.

Source: Medical Xpress

Journal information: Zhenyu Zhang et al, Exposure to Particulate Matter Air Pollution and Anosmia, JAMA Network Open (2021). DOI: 10.1001/jamanetworkopen.2021.11606

Categories : Cancer Immune SystemTags :

Surprising Mechanism of Action Discovered for Stem Cell Drugs

On By ModernMedia
Two cytotoxic T cells (red) attacking an oral squamous cancer cell. Photo by National Cancer Institute on Unsplash

A new study revealed surprising insights into how specialised drugs that regenerate immune cells lost to chemotherapy actually work. 

In cancer patients following chemotherapy, there is a decrease in immune cells because chemotherapy also impacts the stem cells in bone marrow, which were meant to develop into new immune cells. This means that the immune system is then left short of immune cells to fight new infections.

Certain drugs exist, such as plerixafor, that can stimulate the release of stem cells from the bone marrow into the blood stream, so that they can be harvested and then reintroduced into the patients after treatment. These stem cells develop into new immune cells, bolstering the immune system. However, there was a lack of detailed knowledge of how these drugs actually worked.

Now, a study conducted in mice by researchers at the University of Copenhagen demonstrates how the medicine works at the cell level—and, surprisingly, how plerixafor, one of the two applied and tested drugs, is more effective than the other, despite the fact that the other drug, on paper, appears to be the most effective of the two. This discovery may not just help improve stem cell transplantation; it may also lead to improved drugs in the future.

“We have tested two drugs for stem cell transplantation which appear to have the same effect. What they do is block a receptor, causing the bone marrow to release stem cells into the blood. What the new study shows, though, is that they do not just block the receptor; one of the two drugs also affects other signaling pathways in the cell. And in short, that makes it more effective than the other of the two drugs,” explained PhD student Astrid Sissel Jørgensen from the Department of Biomedical Sciences at the University of Copenhagen.

“We used to believe that all we had to do was block the receptor, and that the two drugs had the same effect. It now appears that there is more to it,” she said.

The drugs tested by the researchers mobilise stem cells by acting as CXCR4 receptor antagonists. There are several drugs that target this receptor, including drugs inhibiting HIV replication.

“The drugs not only block the receptor’s normal signaling. One of the two drugs we have tested also affect some of the other cell pathways and even make the receptor withdraw into the cell and disappear from the surface,” explained corresponding author Professor Mette Rosenkilde. The study results revealed that one of the two drugs makes the bone marrow release more stem cells into the blood.

These findings on how the drugs affect cell pathways differently is also known as biased signalling. Mechanisms like these are what make the one drug more effective in practice than on paper, and they challenge the current view of these drugs.

“The results of our study directly influence our view of drugs used for stem cell transplantation. In the long term, though, it may also affect our view of future drugs, and how new drugs should be designed to have the best possible effect, both in connection with stem cell mobilisation, but also for treating HIV infections, where this particular receptor also plays a main role,” said Prof Rosenkilde.

Source: Medical Xpress

Journal information: Astrid S. Jørgensen et al, Biased action of the CXCR4-targeting drug plerixafor is essential for its superior hematopoietic stem cell mobilization, Communications Biology (2021). DOI: 10.1038/s42003-021-02070-9

Categories : AgeingTags :

Lifestyle Interventions Reverse the DNA Methylation Ageing ‘Clock’

On By ModernMedia
Source: Pixabay/CC0

The results of a clinical trial showed that appropriate diet and exercise are able, to some extent, to reverse the DNA methylation ageing ‘clock’.

Lead author Kara Fitzgerald, ND IFMCP, at The Institute for Functional Medicine, explained: “Advanced age is the largest risk factor for impaired mental and physical function and many non-communicable diseases including cancer, neurodegeneration, type 2 diabetes, and cardiovascular disease.”

Methylation clocks are based on systematic methylation changes with age. DNAmAge clock specifically demonstrates about 60% of CpG sites losing methylation with age and 40% gaining methylation.

The researchers conducted a randomised controlled clinical trial conducted among 43 healthy adult males between the ages of 50-72. The 8-week treatment programme included diet, sleep, exercise and relaxation guidance, and supplemental probiotics and phytonutrients.

Genome-wide DNA methylation analysis was conducted on saliva samples using the Illumina Methylation Epic Array and DNAmAge was calculated using the online Horvath DNAmAge clock tool.

The researchers found that the diet and lifestyle treatment resulted in a 3.23 years decrease in DNAmAge compared with controls.

With a strong trend to significance, DNAmAge of those in the treatment group decreased by an average 1.96 years by the end of the program compared to those individuals’ baseline.

Nearly a quarter of the DNAmAge CpG sites are located in glucocorticoid response elements, indicating a likely relationship between stress and accelerated ageing. Cumulative lifetime stress has been shown to be linked to accelerated ageing of the methylome.

Other findings include that PTSD contributes to accelerated methylation age; and that greater infant distress is associated with an underdeveloped, younger epigenetic age.

The researchers tentatively accepted the hypothesis that the methylation pattern, from which the DNAmAge clock is computed, is a driver of ageing, thus they expect that attempting to directly influence the DNA methylome using diet and lifestyle to set back DNAmAge should lead to a healthier, more ‘youthful’ metabolism.

The Fitzgerald Research Team concluded, “it may be that emerging ‘omics’ approaches continue to evolve our understanding of biological age prediction and reversal beyond DNA methylation alone. Integration of our future understanding of multi-omics data should therefore be considered in the future trials of candidate age-delaying interventions.”

Source: Aging

Journal information: Fitzgerald, K. N., et al. (2021) Potential reversal of epigenetic age using a diet and lifestyle intervention: a pilot randomized clinical trial. AGING-US. doi.org/10.18632/aging.202913.

Categories : COVID General InterestTags :

French President Macron in SA for Talks on COVID

On By ModernMedia

French President Emmanuel Macron arrived in South Africa today for talks with President Cyril Ramaphosa on a range of issues including possible technological assistance to aid South Africa’s response to the COVID pandemic.

On the agenda of the visit is the economic, health, research and manufacturing responses to the COVID pandemic.

Arriving from Rwanda, where he acknowledged France’s role in the 1994 genocide, Macron held talks in Pretoria with President Ramaphosa, whom he met last week in Paris at a summit on African economies.

The pair were also due to attend an event to support vaccine production on the continent, sponsored by the European Union, the United States and the World Bank. 

So far South Africa is the country worst hit by COVID on the continent as far available monitoring can determine, and has vaccinated just 1 percent of its population of 59 million people.

South Africa’s immunisation efforts have been hampered by delayed procurement, and then selling off its AstraZeneca vaccines obtained via Covax to other African countries after trial results showed drastically reduced effectiveness against the local B.1.351 variant. Rollout of the replacement Johnson & Johnson vaccine was paused for two weeks in April due to blood clot fears.

Now, along with India, South Africa is campaigning for a waiver of intellectual property rights on COVID vaccines, so that each country may produce its own doses. This effort has met with stiff resistance so far.

Macron has voiced support for a technology transfer to enable vaccine production sites to be set up in poorer countries.

Visit long delayed

Macron’s visit to South Africa has been long delayed due to the COVID pandemic.
The initial purpose for the trip had been to discuss multilateral cooperation with South Africa, an important G20 partner which is also a regular guest at G7 summits.

According to Foreign Policy, the French leader will also seek to establish greater influence in a region that is experiencing greater instability, marked by recent insurgencies in Mozambique.   

Jihadist attacks forced French energy giant Total to suspend work on a multi-billion euro gas project in Cabo Delgado province after a nearby town was targeted.

Before he returns to France, he will pay a visit to the Nelson Mandela Foundation, whose main missions are the fight against AIDS and education in rural areas.

Source: RFI

Categories : Gender Injury & TraumaTags :

Treating Brain Injuries with Sex-specific Interventions

On By ModernMedia

New research has identified a sex-specific window of opportunity to treat traumatic brain injuries (TBIs), which scientists are exploiting in a project to create a sex-targeted drug delivery for TBI.

The study, a collaboration of The University of Texas Health Science Center at Houston (UTHealth) and Arizona State University will be used to help design nanoparticle delivery systems targeting both sexes for treatment of TBI.

“Under normal circumstances, most drugs, even when encapsulated within nanoparticles, do not reach the brain at an effective concentration due to the presence of the blood-brain barrier. However, after a TBI this barrier is compromised, allowing us a window of opportunity to deliver those drugs to the brain where they can have a better chance of exerting a therapeutic effect,” said Rachael Sirianni, PhD, associate professor of neurosurgery at McGovern Medical School at UTHealth. Dr Sirianni’s collaborator and co-lead investigator on this grant, Sarah Stabenfeldt, PhD, was the first to demonstrate that the window of opportunity created in the blood-brain barrier differed between men and women, and it was this key finding that led them to apply for funding.

TBI results from blows to the head, and in the most severe form of TBI, the entirety of the brain is affected by a diffuse type of injury and swelling. The body responds with an acute response to the injury, followed by a chronic phase as it tries to heal.

“In this second phase, a variety of abnormal processes create additional injury that go well beyond the original physical damage to the brain,” Dr Sirianni said.

Normally, the blood vessels maintain a very carefully controlled blood-brain barrier to prevent the entry of harmful substances. However, during this second phase of healing following a TBI, those blood vessels are compromised, possibly allowing substances to seep in.

One of the numerous differences between female and male patients is varying levels and cycles of sex hormones such as oestrogen, progesterone, and testosterone. While these levels already differ in healthy people, additional hormone disruption for both sexes can result from a brain injury.

Dr Sirianni explained that this work is extremely important as presently TBIs have no effective treatment options. Current treatments for TBI vary widely based on injury severity and range from daily cognitive therapy sessions to radical surgery such as bilateral decompressive craniectomies. 

“The goal of this research is to develop different nanoparticle delivery systems that can target the unique physiological state of males versus females following a TBI. Through this research, we hope to develop an optimum distribution system for these drugs to be delivered to the brain and can hopefully find an effective treatment plan for TBIs,” Sirianni said.

Drugs that previously perceived as unsafe or ineffective when given systemically can instead be targeted directly to the injury microenvironment through nanoparticle delivery systems.

“With these nanoparticle systems, we’re looking at how we can revisit a drug that showed promise in preclinical studies or clinical trials but then failed,” Stabenfeldt said.

Source: The University of Texas Health Science Center at Houston

Categories : Cardiovascular Disease New Compounds and TreatmentsTags :

Averting Heart Failure by Shutting Down a Heart Protein

On By ModernMedia
Photo from Olivier Collett on Unsplash
Photo from Olivier Collett on Unsplash

Shutting down a protein found in cardiac muscle could be a new mechanism to treat post-heart attack heart failure, according to research led by the University of Cambridge.

New drugs are needed to improve the heart’s pumping ability after damage from a heart attack. Drugs that strengthen the contraction of failing heart muscle have been deemed unsafe, leaving a gap in the heart attack and heart failure armamentarium.

Researchers now believe that they might have identified a new drug target—a protein called MARK4.

In research funded by the British Heart Foundation (BHF), Cambridge scientists found levels of MARK4 were elevated in mouse hearts after a heart attack. When they compared mice with and without MARK4 in the heart, they found hearts lacking the protein pumped blood 57% more efficiently. This protective effect was seen 24 hours after a heart attack and persisted over the entire follow-up period of four weeks.

The team was first in identifying that MARK4 fine-tunes a structural network within the heart muscle cell—called the microtubule network—that attaches to the machinery governing heart muscle cells contraction and relaxation. When MARK4 levels were increased after a heart attack, microtubules were tightly anchored onto the contractile machinery in the heart, increasing resistance and hindering normal function. When MARK4 levels were reduced, microtubules were loosely anchored, making contraction and relaxation easier.

Following a heart attack the speed of contraction in MARK4-lacking muscle cells increased by 42 percent and the speed of relaxation increased by 47 percent, compared to muscle cells from mice that had the MARK4 protein. They were also almost on par with healthy heart muscle performance, attesting to the power of reducing MARK4.

Based on these findings, the researchers suggested that drugs to switch off MARK4 could be a new way to improve recovery and help the heart to pump blood more efficiently in people with failing hearts.

Dr Xuan Li, BHF Intermediate Research Fellow at University of Cambridge BHF Centre of Research Excellence, said: “After years of research we’ve revealed an entirely new and promising way that could help the recovery of failing hearts.

“It’s early days, and we now need to test the longer-term effects of switching off MARK4. But if drugs to do that prove successful, the life-changing benefits could be seen in people with other types of heart disease as well as those who’ve had a heart attack and developed heart failure.”

Professor Metin Avkiran, Associate Medical Director at the British Heart Foundation, said: “Heart attacks are a major cause of disability worldwide—people who’ve had a major heart attack are at much greater risk of developing chronic heart failure. There are around 920 000 people living with heart failure in the UK, and we desperately need drugs to drastically improve the heart’s function in these patients.

“These findings are a positive step forward. Further research is needed to refine and test drugs that can target MARK4 before we’ll see them given to people who’ve had a heart attack and develop heart failure.”

Source: University of Cambridge