Day: September 26, 2022

Categories : Uncategorized

Protecting the Lungs from Neutrophil Overactivation

On By ModernMedia
Anatomical model of lungs
Photo by Robina Weermeijer on Unsplash

Neutrophils are the body’s first line of defence against infection, which can be activated when foreign pathogens stress the body. When overactivated, neutrophils can damage the body’s own tissues. Lung tissue is saturated with blood vessels, making them very susceptible to neutrophil attacks. If severe enough, acute lung injuries can lead to acute respiratory distress syndrome (ARDS), the leading cause of death due to COVID.

Reporting in JCI Insight, Cold Spring Harbor Laboratory (CSHL) researchers have found a drug candidate that can prevent lethal lung inflammation in mice by inhibiting a protein called PTP1B. Their discovery may help develop better treatments for severe inflammatory conditions like sepsis and COVID.

“When you think about COVID, acute lung injury and ARDS underlie the fatal aspects of the disease,” leader researcher Nicholas Tonks, professor of cancer research says. “And so, when the pandemic took hold, we were wondering whether there was anything we could do to help, to provide an understanding of this aspect of the disease and suggest ways it could be treated.”

Tonks’ graduate student Dongyan Song investigated whether using a PTP1B inhibitor drug candidate could dampen the lethal consequences of overactive neutrophils in mice. She found that pretreating mice with the PTP1B inhibitor reduced lung tissue damage. When untreated, less than half of the mice survived acute lung injuries and ARDS. But when pretreated, they all survived.

The researchers exploited a natural process, called neutrophil aging, that the body uses to control the immune cell’s lifespan. As they age, neutrophils become less dangerous. Tonks’ team discovered PTP1B inhibition speeds up neutrophil aging. “An aged neutrophil is like a soldier without a weapon,” Song explains. “So regardless of how many neutrophils flood an area, they won’t be able to do serious damage.”

Going forward, he and Song are working to increase the understanding of how PTP1B inhibitors affect the immune system. Tonks hopes his lab’s continued research leads to new treatments and preventative measures for various inflammatory diseases.

Tonks’ lab studies signal transduction, the process that controls how cells respond to signals from their environment. In particular, they focus on the PTP protein family, which Tonks discovered over 30 years ago. Since then, he’s sought to develop small molecule drug candidates that target these proteins, which can provide new approaches for treating major human diseases including cancer and metabolic and neurodegenerative diseases.

Source: Cold Spring Harbor Laboratory

Categories : Uncategorized

Newly Found COVID-like Virus in Bats is Vaccine Resistant

On By ModernMedia

Researchers have found that a recently discovered virus in a Russian bat that is similar to SARS-CoV-2 may be able to infect humans and, if it were to spillover, is resistant to current vaccines.

Reporting in PLOS Pathogens, researchers discovered that spike proteins from the bat virus, named Khosta-2, can infect human cells and is resistant to both the monoclonal antibodies and serum from individuals vaccinated for SARS-CoV-2. Both Khosta-2 and SARS- CoV-2 belong to the same sub-category of coronaviruses known as sarbecoviruses.

“Our research further demonstrates that sarbecoviruses circulating in wildlife outside of Asia – even in places like western Russia where the Khosta-2 virus was found – also pose a threat to global health and ongoing vaccine campaigns against SARS-CoV-2,” said Michael Letko, WSU virologist and corresponding author of the study.

Letko said the discovery of Khosta-2 highlights the need to develop universal vaccines to protect against sarbecoviruses in general, rather than just against known variants of SARS-CoV-2. 

“Right now, there are groups trying to come up with a vaccine that doesn’t just protect against the next variant of SARS-2 but actually protects us against the sarbecoviruses in general,” Letko said. “Unfortunately, many of our current vaccines are designed to specific viruses we know infect human cells or those that seem to pose the biggest risk to infect us. But that is a list that’s everchanging. We need to broaden the design of these vaccines to protect against all sarbecoviruses.”

While hundreds of sarbecoviruses have been discovered in recent years, predominantly in bats in Asia, the majority are not capable of infecting human cells. The Khosta-1 and Khosta-2 viruses were discovered in Russian bats in late 2020, and it initially appeared they were not a threat to humans.

“Genetically, these weird Russian viruses looked like some of the others that had been discovered elsewhere around the world, but because they did not look like SARS-CoV-2, no one thought they were really anything to get too excited about,” Letko said. “But when we looked at them more, we were really surprised to find they could infect human cells. That changes a little bit of our understanding of these viruses, where they come from and what regions are concerning.”

Letko teamed with a pair of researchers in Washington State University’s to study the two newly discovered viruses. They determined Khosta-1 posed low risk to humans, but Khosta-2 demonstrated some troubling traits.

The team found that like SARS-CoV-2, Khosta-2 can use its spike protein to infect cells by attaching to a receptor protein, called angiotensin converting enzyme 2 (ACE2), found throughout human cells. They next set out to determine if current vaccines protect against the new virus.

Using serum derived from COVID-vaccinated human populations, the team saw that Khosta-2 was not neutralised by current vaccines. They also tested serum from people who were infected with the omicron variant, but the antibodies, too, were ineffective.

Fortunately, Letko said the new virus is lacking some of the genes believed to be involved in pathogenesis in humans. There is a risk, however, of Khosta-2 recombining with a second virus like SARS-CoV-2.

“When you see SARS-2 has this ability to spill back from humans and into wildlife, and then there are other viruses like Khosta-2 waiting in those animals with these properties we really don’t want them to have, it sets up this scenario where you keep rolling the dice until they combine to make a potentially riskier virus,” Letko said.

Source: Washington State University

Categories : New Compounds and TreatmentsTags :

Harnessing Metals to Fight Fungal Infections

On By ModernMedia
Source: NCI

Even as new, drug-resistant fungal strains are being detected, the development of new antifungal drugs has reached a virtual standstill in recent years. Today, only around a dozen clinical trials are underway with new active agents for the treatment of fungal infections. A new drug discovery effort, reported in JACS Au, has identified a range of metal compounds that are highly effective as antifungals, but mistrust around using metals in drugs remains.

“In comparison with more than a thousand cancer drugs that are currently being tested on human subjects, this is an exceptionally small number,” explains Dr Angelo Frei of the Department of Chemistry, Biochemistry and Pharmacy at the University of Bern, lead author of the study.

To encourage the development of anti-fungal and antibacterial agents, researchers at the University of Queensland in Australia have founded the Community for Open Antimicrobial Drug Discovery, or CO-ADD. The ambitious goal of the initiative is to find new antimicrobial active agents by offering chemists worldwide the opportunity to test any chemical compound against bacteria and fungi at no cost. As Frei explains, the initial focus of CO-ADD has been on “organic” molecules, which mainly consist of the elements of carbon, hydrogen, oxygen and nitrogen, and do not contain any metals.

However, Frei, who is trying to develop new metal-based antibiotics with his research group at the University of Bern, has found that over 1000 of the more than 300 000 compounds tested by CO-ADD contained metals. “For most folks, when used in connection with the word ‘people’, the word metal triggers a feeling of unease. The opinion that metals are fundamentally harmful to us is widespread. However, this is only partially true. The decisive factor is which metal is used and in which form,” explains Frei, who is responsible for all the metal compounds in the CO-ADD database.

In their new study, the researchers turned their attention to the metal compounds which showed activity against fungal infections. Here, 21 highly-active metal compounds were tested against various resistant fungal strains. These contained the metals cobalt, nickel, rhodium, palladium, silver, europium, iridium, platinum, molybdenum and gold. “Many of the metal compounds demonstrated a good activity against all fungal strains and were up to 30 000 times more active against fungi than against human cells,” explains Frei. The most active compounds were then tested in a model organism, the larvae of the wax moth. The researchers observed that just one of the eleven tested metal compounds showed signs of toxicity, while the others were well tolerated by the larvae. In the next step, some metal compounds were tested in an infection model, and one compound was effective in reducing the fungal infection in larvae.

Considerable potential for broad application

Metal compounds are not new to the world of medicine: Cisplatin, for example, which contains platinum, is one of the most widely used anti-cancer drugs. Despite this, there is a long way to go before new antimicrobial drugs that contain metals can be approved. “Our hope is that our work will improve the reputation of metals in medical applications and motivate other research groups to further explore this large but relatively unexplored field,” says Frei. “If we exploit the full potential of the periodic table, we may be able to prevent a future where we don’t have any effective antibiotics and active agents to prevent and treat fungal infections.”

Source: University of Bern

Categories : Ageing Cardiovascular DiseaseTags :

More Older Adults Should Monitor Blood Pressure at Home

On By ModernMedia
Blood pressure cuff
BP cuff for home monitoring, Source: Pixabay

Only 48% of people age 50 to 80 taking blood pressure medications or have a health condition affected by hypertension regularly check their blood pressure at home or other places, found a new study published in JAMA Network Open.

A somewhat higher number (62%) say a health care provider encouraged them to perform such checks. Poll respondents whose providers had recommended they check their blood pressure at home were three and a half times more likely to do so than those who didn’t recall getting such a recommendation.

The findings underscore the importance of exploring the reasons why at-risk patients aren’t checking their blood pressure, and why providers aren’t recommending they check — as well as finding ways to prompt more people with these health conditions to check their blood pressure regularly. This could play an important role in helping patients live longer and maintain heart and brain health, the study’s authors say.

Past research has shown that regular home monitoring can help with blood pressure control, and that better control can mean reduced risk of death; of cardiovascular events including strokes and heart attacks; and of cognitive impairment and dementia.

A team from Michigan Medicine, the University of Michigan’s academic medical centre, conducted the research. The data come from the National Poll on Healthy Aging and build on a report issued last year.

The poll, based at the U-M Institute for Healthcare Policy and Innovation and supported by Michigan Medicine and AARP, asked adults aged 50 to 80 about their chronic health conditions, blood pressure monitoring outside of clinic settings, and interactions with health providers about blood pressure. Study authors Mellanie V. Springer, M.D., M.S., of the Michigan Medicine Department of Neurology, and Deborah Levine, M.D., M.P.H., of the Department of Internal Medicine, worked with the NPHA team to develop the poll questions and analyze the findings.

The data in the new paper come from the 1,247 respondents who said they were either taking a medication to control their blood pressure or had a chronic health condition that requires blood pressure control — specifically, a history of stroke, coronary heart disease, congestive heart failure, diabetes, chronic kidney disease or hypertension.

Of them, 55% said they own a blood pressure monitor, though some said they don’t ever use it. Among those who do use it, there was wide variation in how often they checked their pressure — and only about half said they share their readings with a health provider. But those who own a monitor were more than 10 times more likely to check their blood pressure outside of health care settings than those who don’t own one.

The authors note that blood pressure monitoring is associated with lower blood pressure and is cost-effective. They say that the results suggest that protocols should be developed to educate patients about the importance of self blood pressure monitoring and sharing readings with clinicians.

Source: Michigan Medicine – University of Michigan

Categories : AddictionTags :

Cortisol Levels may Predict Addiction Recovery Success

On By ModernMedia
Depression, young man
Source: Andrew Neel on Unsplash

A new study found that lower initial cortisol levels may serve as a predictor for retention in treatment programs for substance use disorder.

The prospective observational study examined the salivary cortisol, stress exposure, adverse childhood experiences (ACEs) and treatment retention of males enrolled in abstinence-based, residential alcohol and drug recovery programs. Their findings were published last month in Alcoholism: Clinical and Experimental Research.

Cortisol levels reflect a physiological response to stress. In this case, researchers found that participants who remained in the treatment program less than 90 days had significantly higher initial cortisol levels than those who remained in the program longer than 90 days. Further, a Cox proportional hazards model indicated that elevated salivary cortisol, marital/relationship status and ACEs score correlated significantly with hazards of discontinuing the program early.

“Our hope is that these findings will lead to cortisol as a biomarker that can help clinicians determine which individuals might need a more intensive therapeutic approach,” said Todd H. Davies, Ph.D., associate director of research and development at the Joan C. Edwards School of Medicine and corresponding author on the study.

In collaboration with Recovery Point, the researchers have a larger follow-up study underway that seeks to identify the clinical significant levels of cortisol. This expanded study also includes a more representative population and examine the hormone oxytocin.

Source: Marshall University Joan C. Edwards School of Medicine