Month: October 2024

Categories : Diseases, Syndromes and Conditions HospitalsTags :

Chemists Discover Alarming Resistance of P. Aeruginosa to Common Cleaners

On By ModernMedia
Photo by Matilda Wormwood

A new study reveals widespread resistance of a major bacterial pathogen to the active ingredients in cleaning agents commonly used in hospitals and homes. The American Chemical Society Infectious Diseases published the research led by chemists at Emory University. It demonstrates the surprising level of resistance to cleaning agents of multidrug-resistant Pseudomonas aeruginosa, a pathogen of particular concern in hospital settings.

The study also identifies biocides that are highly effective against P. aeruginosa, including a novel compound developed at Emory in collaboration with Villanova University. The researchers describe how these biocides work differently than most disinfectants currently in use.

“We hope our findings can help guide hospitals to reconsider protocols for the sanitation of patient rooms and other facilities,” says William Wuest, Emory professor of chemistry and a senior author of the study. “We also hope that our findings of a new mechanism of action against these bacterial strains may help in the design of future disinfectant products.”

First authors of the study are Christian Sanchez (who did the work as an Emory PhD student in chemistry and, following graduation, joined the faculty at Samford University) and German Vargas-Cuebas, an Emory PhD candidate in microbiology through Laney Graduate School.

“Resistance of pathogens to cleaning agents is an area that’s often overlooked,” Vargas-Cuebas says, “but it’s an important area of study, especially with the rise in antibiotic-resistant pathogens worldwide.”

Kevin Minbiole, professor of chemistry at Villanova, is co-senior author of the paper.

Workhorse disinfectants losing steam

Quaternary ammonium compounds, or QACs, are active ingredients commonly seen in household and hospital cleaners, including some disinfectant sprays and liquids, antibacterial sanitizing wipes and soaps.

“There are a handful of QACs that have been the workhorse disinfectants for around 100 years, on the frontline of most homes and hospitals,” Wuest says. “Very little has been done to modify their structures because they have long worked so well against many common bacteria, viruses, molds and fungi and they’re so simple and cheap to make.”

The Wuest lab is a leader in studies of QACs and other disinfecting agents. One issue Wuest and his colleagues have identified is that some bacterial strains are developing resistance to QACs. That trend could cause serious problems for sanitation in hospitals.

A pathogen of critical priority

More than 2.8 million antimicrobial-resistant infections occur in the United States each year, leading to more than 35,000 deaths, according to the Centers for Disease Control and Prevention (CDC).

The CDC names multidrug-resistant P. aeruginosa as one of seven pathogens causing infections that increased in the United States during the COVID-19 pandemic and remain above prepandemic levels.

Worldwide, P. aeruginosa causes more than 500,000 deaths annually and has been named a pathogen of critical priority by the World Health Organization.

P. aeruginosa is commonly found in the environment, including in soil and freshwater. Reservoirs in hospital settings can include drains, taps, sinks and equipment washers.

While the bacterium generally does not affect healthy people it can cause infections in individuals with cystic fibrosis and those who are immunocompromised, such as patients with burns, cancer and many other serious conditions. Patients with invasive devices such as catheters are also at risk due to the ability of P. aeruginosa to form biofilms on the surfaces of these devices.

P. aeruginosa, like other gram-negative bacteria, is enclosed in a second, fatty outer membrane that acts as a protective capsule, making it more difficult to kill.

How QACs kill

QACs have a nitrogen atom at the center of four carbon chains. In simplest terms, the positively charged head of the nitrogen center is drawn to the negatively charged phosphates of the fatty acids encasing P. aeruginosa and many other bacteria and viruses. The heads of the carbon chains act like spearpoints, stabbing into both protective fatty membranes and inner cellular membranes and causing pathogens to disintegrate.

The researchers tested 20 different drug-resistant strains of P. aeruginosa collected from hospitals around the world by the Walter Reed National Military Medical Center as part of the Multidrug-Resistant Organism Repository and Surveillance Network.

The results showed that all 20 strains were at least partially resistant to QACs — the common active ingredient in most front-line cleaning agents — and 80% of the strains were fully resistant to QACs.

“This mechanism has worked for 100 years essentially by slicing into the outer and inner membranes of a pathogen and destroying them,” Wuest says. “We were surprised to see the level at which that appears to no longer be the case.”

Improper use of cleaning agents may be one factor leading to resistance, Wuest theorizes.

“QACs don’t immediately kill,” he explains. “After application, it’s important to wait four or five minutes before wiping these cleaning agents away. It’s also important to use the right concentration. If used inappropriately, some bacteria can survive, which can lead to them developing resistance.”

Greater use of cleaning agents during the COVID-19 pandemic may have given P. aeruginosa and some other hard-to-kill pathogens more opportunities to develop resistance, he adds.

A new method that ‘works surprisingly well’

For the current paper, the researchers also tested the resistance of the panel of multidrug-resistant P. aeruginosa strains against a new quaternary phosphonium compound, or QPC, developed in the Wuest and Minbiole labs. The results showed that the compound was highly effective at killing all 20 of the resistant P. aeruginosa strains.

“It works surprisingly well even at a low concentration,” Vargas-Cuebas says.

The researchers demonstrated that their novel QPC works not by piercing the protective outer capsule of a P. aeruginosa bacterium but by diffusing through this outer membrane and then selectively attacking the inner cellular membrane.

“It’s counterintuitive,” Wuest remarks. “You would think that the approach of conventional biocides, to take out both membranes, would be a more effective way to kill P. aeruginosa. Why does passively diffusing through the outer membrane and focusing on attacking the inner membrane make our QPC compound more effective? We don’t know yet. It’s like a magic trick.”

They showed that this same mechanism underlies the effectiveness of two commercial antiseptics: octenidine, more commonly used in Europe as a hospital antiseptic, and chlorhexidine, a common ingredient in mouthwashes.

Wuest and colleagues plan to continue research into how this newly identified mechanism may work against an array of pathogens and how that might translate into new biocides and more effective cleaning protocols in hospitals and other settings.

“Our work is paving the way for much-needed innovations in disinfectant research,” Wuest says.

Source: Emory University

Categories : Medical IndustryTags :

Merck Foundation Wins Most Influential NGO of 2024 for Efforts Shaping Africa’s Future

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Photo by Hush Naidoo on Unsplash

Merck Foundation, the philanthropic arm of Merck KGaA Germany has been awarded as the “NGO of the Year 2024”, the Most Influential NGO Shaping Africa’s Future and Leading Community Empowerment, by Avance Media, a leading rating and voting firm in Africa.

On receiving the accolade, Senator, Dr. Rasha Kelej, CEO of Merck Foundation and One of 100 Most Influential Africans for five consecutive years – from 2019 till 2023 expressed, “I am thrilled and proud to share that Merck Foundation has been voted as the “NGO OF THE YEAR 2024”, out of the list of 10 NGOs Leading Community Empowerment in Africa, shortlisted by Avance Media, big thanks for everyone who voted for us, we would not have been able to make it without your support and trust in Merck Foundation’s significant role in shaping the future of African communities.”

Winning the “NGO of the Year 2024 ” as per people’s votes acknowledged their collective efforts in shaping Africa’s future through key sectors such as health, education, and economic empowerment.

“This recognition inspires me and my team to continue our mission to transform the patient care landscape, drive cultural change, support girls’ education, empower women, and break the stigma around infertility in Africa and beyond. We are committed to contributing to improving lives of the people.” Dr. Rasha Kelej added.

Merck Foundation was initially announced as one of 10 Most Influential NGOs Shaping Africa’s Future, along with other leading NGOs working in Africa like Save the Children, Plan International, Doctors without Borders, Africa Women’s Development Fun, African Medical & Research Foundation, and others. Merck Foundation was then voted for as the NGO of the Year 2024, out of the 10 NGOs listed.

Since 2012, Merck Foundation, together with their Ambassadors, the First Ladies of Africa, and Partners like Ministries of Health, Gender, Education, and Communication, continues to transform patient care across Africa and bring cultural shift with regards to a wide range of social and health issues, including breaking the stigma around infertility, supporting girls’ education, ending child marriage and FGM, stopping gender-based violence, and raising awareness about diabetes and hypertension.

“I am happy to share that we have provided more than 2080 scholarships to young doctors from 52 countries, in 44 underserved medical specialties. Many of our Merck Foundation Alumni are becoming the first specialists in their countries. Together, we continue to make history,” Dr. Kelej added.

The scholarships of one year, two year and three year fellowship, diploma and master course have been provided in 44 underserved medical specialties like Oncology, Diabetes, Cardiology, Endocrinology, Respiratory, Acute Medicine, Sexual and Reproductive medicine, Embryology, Respiratory, Critical care, Psychiatry, General Surgery, Dermatology, Emergency and Resuscitation Medicine, Gastroenterology, Neuroimaging for Research, Pain Management, Neonatal Medicine, Clinical Microbiology & Infectious Diseases, Advanced Surgical Practice and more.

Through their “More Than a Mother” campaign which is a strong movement that aims to empower infertile and childless women through access to information, education and change of mindset, Merck Foundation has been building quality and equitable reproductive and fertility care capacity, breaking infertility stigma and raising awareness about Infertility Prevention and Male Infertility.

“I am happy that we are contributing to building and advancing fertility care capacity in Africa and improving better access to women’s health. I am very proud to share that we have provided till today more than 650 scholarships of Embryology, Fertility and Reproductive care to young doctors from 39 different countries. Moreover, we also support childless women by helping them start their own small businesses. It is all about giving every woman the respect and support she deserves to lead a fulfilling life, with or without a child”, Senator, Rasha Kelej explained.

Moreover, Merck Foundation strongly believe that Education is one of the most critical areas of women empowerment. Therefore, through their “Educating Linda”, Merck Foundation contributes to the future of young African girls who are brilliant but underprivileged, by providing more than 700 scholarships, to cover their school  fees till they graduate, and thousands of school items to schoolgirls in many African countries including Botswana, Burundi, Malawi, Ghana, The Gambia, Nigeria, Zambia, Zimbabwe, Ghana, Namibia, Democratic Republic of the Congo, Niger and more.

I am happy that we are contributing to building and advancing fertility care capacity in Africa and improving better access to women’s health

Dr. Rasha Kelej

Additionally, Merck Foundation has been raising awareness about many critical social issues including breaking infertility stigma, supporting girl education, women empowerment, ending FGM & child marriage, stopping GBV and important health issues like Diabetes & Hypertension prevention, early detection & Management; promoting healthy lifestyle; infertility awareness & management and more. Merck Foundation has introduced many unique and innovative ways like Songs, Animation Films, Children Storybooks, Health Media Trainings, “Our Africa” TV Program, Awards for Media, Filmmakers, Fashion Designers and Musicians and more.

Source: Merck Foundation

Categories : Expert Opinion Healthcare Politics and RegulationsTags :

NHI Offers an Opportunity to Boost Primary Healthcare – We Must Seize it

On By ModernMedia

By Russell Rensburg

To see National Health Insurance primarily as the setting up of a state-run medical aid scheme risks underplaying its massive potential to restructure how public healthcare services are organised and funded, and with that, its potential to boost the delivery of primary healthcare services in South Africa, argues Russell Rensburg.

It has been 30 years since South Africa emerged from centuries long racial suppression and state-sponsored apartheid and took her place among the community of sovereign, democratic nations. In 1996, we adopted the final Constitution, in which we committed to addressing the injustices of the past and building a society based on social justice and human dignity. That promise is carried through in the Bill of Rights, which under Section 27 includes the right to healthcare, food, and social assistance. The right to access healthcare services, like many socio-economic rights, is subject to the state taking reasonable legislative and other measures within available resources to progressively realise the right.

Pursuant to this, the National Health Act, which provides the framework for a structured uniform health system within the country, was adopted in 2003. The Act assigns the minister of health the obligation to ensure the provision of essential health services, which must include primary healthcare services. But, to date, no health minister has published regulations that define the exact scope of essential health services, nor has a framework been offered for the development of a defined package of care to be provided within the resources available.

The result is that, despite significant investments in public funded healthcare, the system and the services it provides has largely been shaped by existing infrastructure inequity. Put differently, health investments have typically gone where the infrastructure exists, rather than being guided by providing a defined package of primary healthcare services in all the places where it is most needed.

In the near term, the health system faces several immediate challenges. Per capita spending is declining. Spending is biased towards hospitals, with 42% of the national health budget spent on central and provincial hospitals. Another problem is that health service planning and budgets do not sufficiently account for our changing demographic profile –  life expectancy has increased and we have a growing population of young people.

The National Health Insurance (NHI) Act is an attempt to address this through the establishment of the national health insurance fund, which initially will be the only purchaser of public sector healthcare services. Broadly, the NHI aims to pool funds to provide access to good quality, affordable healthcare services for all South Africans and certain foreign nationals, based on their health needs and irrespective of their socio-economic status.

This shift marks a substantial change from the existing setup, where 85% of the national health budget is allocated at the provincial level. In South Africa, the share provinces get of the national budget is largely determined by the equitable share formula. The health component of the formula includes a number of variables to account for healthcare need, including premature mortality (as a proxy for unmet need ), multi index deprivation (to account for social determinants of health such as poverty ), income, housing, and measures of sparsity (to account for rurality). But the biggest driver of funding is historical utilisation, which shapes resource allocation at the provincial level. The result is that the funding is overly focused on providing care under the existing systems, rather than progressively expanding access to healthcare, and boosting access to primary care in particular.

In short, NHI represents a major shift away from this paradigm by which provinces receive healthcare funds via the equitable share and based on historic spending.

How it will work

Under NHI, the public sector will budget according to level of care, initially prioritising the district health system through the establishment of district health management offices. These offices will support contracting units for primary care, which will comprise a district hospital, community health centres , primary healthcare clinics, and ward based outreach teams as well as provisions for integrated practice comprising GPs, pharmacists, dentists, and rehab professionals (occupational health, physiotherapy, and speech therapy). The district health management offices will be responsible for the achievement of health outcomes in districts.

In theory, this will allow for healthcare priorities to be shaped at the district level and for services to be more responsive to the healthcare needs of communities. For example, a district like OR Tambo could prioritise more resources towards addressing maternal mortality by expanding ante-natal services or developing responses to address the health access gaps for older people in rural areas. In urban districts, like the City of Johannesburg, it could prioritise expanding access to reproductive health services by contracting in private health providers who are better placed to respond to the needs of working women. Ultimately, such a shift to a more responsive and more localised health system could also help increase uptake of TB and HIV prevention and treatment services across the board.

How to get the ball rolling

Reorientating our health system towards primary healthcare will be a difficult and time-consuming process, given the complex nature of health systems. But, there are things we can do right away to get things moving. We don’t have to wait for full implementation of NHI.

The current District Health Programme Grant can be expanded to enable provinces to increase primary healthcare services. The grant currently focuses on resourcing the country’s response to HIV, which seems to have reached a plateau with fewer people initiated on treatment. Contracting in private providers using this grant could improve service accessibility for testing, reproductive health services and routine healthcare for the working poor. Indeed, contracting in non-state healthcare providers, such as healthcare NGOs, pharmacies, and GPs, can significantly improve the patient experience and help build the public trust that is needed for NHI. As we repurpose the District Health Programme Grant, we can also start building the systems we will need for the district health management offices envisaged under NHI, thus helping to ease the transition when it comes.

The biggest immediate opportunity however lies in improving the accessibility and acceptability of district health services for the working poor. A study by the Bureau of Market Research at UNISA estimated that around 75% of working people in South Africa earn less than R6 000 a month. The current structure of publicly funded primary healthcare services do not respond to their routine needs, which include accessing family planning, seeing a GP when ill, a dentist to address oral health issues or access to rehab services. Apart from meeting the needs of these people, expanding service points, particularly in urban areas, can also improve disease surveillance through increased testing, and increased uptake of HIV prevention and treatment services.

There are more areas where we can make progress now that will ease the transition to NHI. For example, the current National Tertiary Services Grant, with an allocation of R15 billion, can be used to support a deep dive into what services our hospitals offer, what resources they are allocated and why, and how all of that lines up with the health need in our districts. The data isn’t currently there to really know whether we are getting value for money from our public hospitals. As with primary care, we need to get a clearer understanding of the need and start re-engineering the system so that we are in a better position to meet that need as we start implementing NHI.

Ultimately then, it is limiting to think of NHI exclusively as the establishment of a state-run medical aid scheme – as it is often portrayed in the media. A public discourse dominated by debates over the future of medical schemes risks obscuring the substantial potential NHI offers for improving and restructuring how public health services are organised and funded. The reality is that with NHI, we have an opportunity to shift the focus of our healthcare system toward primary healthcare and in the process to make our health system much more efficient and equitable. It is imperative that we do whatever is needed to deliver on that potential.

*Rensburg is Director of the Rural Health Advocacy Project.

Note: Spotlight aims to deepen public understanding of important health issues by publishing a variety of views on its opinion pages. The views expressed in this article are not necessarily shared by the Spotlight editors.

Republished from Spotlight under a Creative Commons licence.

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Categories : Cardiovascular Disease Lab Tests and ImagingTags :

New Blood Test on a Chip Rapidly Detects Earliest Signs of Heart Attack

On By ModernMedia
Peng Zheng shows off the heart of the blood test, chip with a groundbreaking nanostructured surface on which blood is tested. Image: Will Kirk / Johns Hopkins University

With heart attacks, every second counts. A newly developed blood test on a chip diagnoses them in minutes rather than hours and could be adapted as a tool for first responders and people at home.

“Heart attacks require immediate medical intervention in order to improve patient outcomes, but while early diagnosis is critical, it can also be very challenging – and near impossible outside of a clinical setting,” said lead author Peng Zheng, an assistant research scientist at Johns Hopkins University. “We were able to invent a new technology that can quickly and accurately establish if someone is having a heart attack.”

The proof-of-concept work, which can be modified to detect infectious diseases and cancer biomarkers, is described in Advanced Science.

Zheng and senior author Ishan Barman develop diagnostic tools through biophotonics, using laser light to detect biomarkers, which are bodily responses to conditions including disease. Here they used the technology to find the earliest signs in the blood that someone was having a heart attack. Heart attacks remain one of the trickiest conditions to diagnose, with symptoms that vary widely and biological signals that can be subtle and easy to miss in the early stages of an attack, when medical intervention can do the most good.

Will be like ‘ Star Trek tricorder’

People suspected of having heart attacks typically are given a combination of tests to confirm the diagnosis – usually starting with electrocardiograms to measure the electrical activity of the heart, a procedure that takes about five minutes, and blood tests to detect the hallmarks of a heart attack, where lab work can take at least an hour and often has to be repeated.

The stand-alone blood test the team created provides results in five to seven minutes. It’s also more accurate and more affordable than current methods, the researchers say.

Though created for speedy diagnostic work in a clinical setting, the test could be adapted as a hand-held tool that first responders could use in the field, or that people might even be able to use themselves at home.

“We’re talking about speed, we’re talking about accuracy, and we’re talking of the ability to perform measurements outside of a hospital,” said Barman, a bioengineer in JHU’s Department of Mechanical Engineering. “In the future we hope this could be made into a hand-held instrument like a Star Trek tricorder, where you have a drop of blood and then, voilà, in a few seconds you have detection.”

The heart of the invention is a tiny chip with a groundbreaking nanostructured surface on which blood is tested. The chip’s “metasurface” enhances electric and magnetic signals during Raman spectroscopy analysis, making heart attack biomarkers visible in seconds, even in ultra-low concentrations. The tool is sensitive enough to flag heart attack biomarkers that might not be detected at all with current tests, or not detected until much later in an attack.

Though designed to diagnose heart attacks, the tool could be adapted to detect cancer and infectious diseases, the researchers say.

“There is enormous commercial potential,” Barman said. “There’s nothing that limits this platform technology.”

Next the team plans to refine the blood test and explore larger clinical trials.

Source: John Hopkins University

Categories : OphthalmologyTags :

The Search for an Effective Treatment for Glaucoma

On By ModernMedia
Photo by Ksenia Chernaya

Pete Williams at Karolinska Institutet is one of the few researchers in Sweden concentrating on glaucoma. The goal is an effective treatment, something that stops the degenerative process in the nerve cells of the eye. He is the senior author of a new paper in Nature Communications on how deficiency of the enzyme NMNAT2 renders the nerve cells of the eye vulnerable to neurodegeneration and could be a key in the search for a treatment. 

Glaucoma is very common. Eighty million people worldwide have the eye disease. There is no cure, but there are treatments that lower the pressure in the eye and that can slow down the progression of the disease, which otherwise leads to irreversible blindness.

Not always treatable

“Most people who have heard of glaucoma believe that it can be treated with eye drops and surgery. Unfortunately, this is not entirely true. For many of the patients, the treatment lower the eye pressure but doesn’t prevent further vision loss,” says Pete Williams.

Knowledge about glaucoma has taken time to develop because the disease progresses slowly. This means that in the past, it took many years before researchers could see if a particular treatment had any effect. However, in the last decade or so, the availability of instruments that measure changes in the eye much earlier than the patient experiences them has given new impetus to research into the eye disease.

The importance of NAD

In the 1980s, research into neurodegenerative diseases discovered a link with NAD, a co-enzyme, ie a molecule that binds to an enzyme and makes it active.  Pete Williams’ group was the first to show that NAD levels were low in animal models of glaucoma.

“NAD has many important functions in the body. A lack of it is important for neuronal health and survival in many diseases, but we don’t yet know how to use this information to create a better treatment ” says Pete Williams.

When the body makes NAD, it uses an enzyme NMNAT1. However, in neurons, it needs another enzyme: NMNAT2 (which is only found in neurons). 

“In our recent paper in Nature Communications, we show that NMNAT2 is needed to protect neurons in the eye and that gene therapy can be used to increase levels,” says Pete Willams. “

The research team is now moving on to try to develop new substances that target NMNAT2 in nerve cells. 

Source: Karolinksa Institutet

Categories : Cancer ExerciseTags :

Aerobic Exercise may Help Prevent the Brain Fog from Chemotherapy

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Clinical trial reveals improved self-reported cognitive function in women with breast cancer who started an exercise program when initiating chemotherapy.

Photo by Ketut Subiyanto on Pexels

Many women who receive chemotherapy experience a decreased ability to remember, concentrate, and/or think – commonly referred to as “chemo-brain” or “brain fog” – both short- and long-term. In a recent clinical trial of women initiating chemotherapy for breast cancer, those who simultaneously started an aerobic exercise program self-reported greater improvements in cognitive function and quality of life compared with those receiving standard care. The findings are published by Wiley online in CANCER, a peer-reviewed journal of the American Cancer Society.

The study, called the Aerobic exercise and CogniTIVe functioning in women with breAsT cancEr (ACTIVATE) trial, included 57 Canadian women in Ottawa and Vancouver who were diagnosed with stage I–III breast cancer and beginning chemotherapy. All women participated in 12–24 weeks of aerobic exercise: 28 started this exercise when initiating chemotherapy and 29 started after chemotherapy completion. Cognitive function assessments were conducted before chemotherapy initiation and after chemotherapy completion (therefore, before the latter group started the exercise program).

Women who participated in the aerobic exercise program during chemotherapy self-reported better cognitive functioning and felt their mental abilities improved compared with those who received standard care without exercise. Neuropsychological testing – a performance-based method used to measure a range of mental functions – revealed similar cognitive performance in the two groups after chemotherapy completion, however.

“Our findings strengthen the case for making exercise assessment, recommendation, and referral a routine part of cancer care; this may help empower women living with and beyond cancer to actively manage both their physical and mental health during and after treatment,” said lead author Jennifer Brunet, PhD, of the University of Ottawa.

Dr Brunet noted that many women undergoing chemotherapy for breast cancer remain insufficiently active, and there are limited exercise programs tailored to their needs. “To address this, we advocate for collaboration across various sectors – academic, healthcare, fitness, and community – to develop exercise programs specifically designed for women with breast cancer,” she said. “These programs should be easy to adopt and implement widely, helping to make the benefits of exercise more accessible to all women facing the challenges of cancer treatment and recovery.”

Source: Wiley

Categories : Metabolic DisordersTags :

How Muscle Energy Production is Impaired in Type 2 Diabetes

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Mitochondria (red) are organelles found in most cells. They generate a cell’s chemical energy. Credit: NICHD/U. Manor

A new study from Karolinska Institutet, published in Science Translational Medicine, shows that people with type 2 diabetes have lower levels of the protein that breaks down and converts creatine in the muscles. This leads to impaired function of the mitochondria, the ‘powerhouses’ of the cell.

Creatine is a popular supplement for improving exercise performance as it can make muscles work harder and longer before they become fatigued. Previous studies however showed a possible link between high blood creatine levels and increased type 2 diabetes risk. This has raised questions about whether creatine supplementation may contribute to that risk.

New research based on studies in both humans and mice shows that people with type 2 diabetes have lower protein levels in their muscles that metabolises and converts creatine – a protein called creatine kinase. 

“This reduced protein level leads to impaired creatine metabolism in the muscle. This may explain why people with type 2 diabetes accumulate creatine in their blood,” says principal investigator Anna Krook, Professor at the Department of Physiology and Pharmacology at Karolinska Institutet.

Scientists don’t know exactly what high creatine levels in the blood mean for the body, but it is known that it does have an effect outside the cells. 

“The findings indicate that impaired creatine metabolism is a consequence of type 2 diabetes, rather than a cause of the disease,” says Anna Krook. 

Impairs mitochondrial function

The study also shows that low levels of creatine kinase are not only linked to higher creatine levels in the blood, but also impair the function of mitochondria in the muscle. Mitochondria, which convert nutrients into energy, function less well in muscle cells with reduced creatine kinase, leading to both lower energy production and increased cell stress.

“This is quite consistent with the fact that people with type 2 diabetes have poorer energy metabolism. In the future, one possibility could be to regulate creatine kinase as part of the treatment of metabolic diseases such as obesity and diabetes,” says Anna Krook.

An unexpected finding of the study was that changes in creatine kinase levels affected the appearance of mitochondria and also their ability to produce energy, regardless of the amount of creatine available. 

“This suggests that although the main role of creatine kinase is to process creatine, it affects mitochondrial function in other ways,” explains David Rizo-Roca, the study’s first author.

“Our next step is to find the molecular mechanisms behind these effects,” he says. 

Source: Karolinska Institutet

Categories : Cardiovascular DiseaseTags :

Immunotherapy Blocks Scarring, Improves Cardiac Function in Heart Failure

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Right side heart failure. Credit: Scientific Animations CC4.0

A new study from Washington University School of Medicine in St. Louis suggests that a type of immunotherapy also may be an effective treatment strategy for heart failure by using an FDA-approved drug to block the signalling protein IL-1 beta. The study is published in Nature.

After a heart attack, viral infection or other injury to the heart, scar tissue often forms in the heart muscle, where it interferes with the heart’s normal contractions and plays a leading role in heart failure, a chronic condition which can only be slowed, not cured.

Studying human tissue samples as part of the new study, the researchers identified a type of fibroblast cell in the heart as the main culprit responsible for the formation of scar tissue in heart failure. To see if they could prevent scar formation, the scientists turned to mouse models of heart failure that have the very same type of fibroblasts. They used a therapeutic monoclonal antibody that blocks the formation of this harmful type of fibroblast, and succeeded in reducing the formation of scar tissue and improving heart function in the mice.

“After scar tissue forms in the heart, its ability to recover is dramatically impaired or impossible,” said cardiologist and senior author Kory Lavine, MD, PhD, a professor of medicine in the Cardiovascular Division at WashU Medicine. “Heart failure is a growing problem in the US and globally, affecting millions of people. Current treatments can help relieve symptoms and slow the progression, but there is a tremendous need for better therapies that actually stop the disease process and prevent the formation of new scar tissue that causes a loss of heart function. We are hopeful our study will lead to clinical trials investigating this immunotherapy strategy in heart failure patients.”

Fibroblasts have many roles in the heart, and parsing out the differences between various populations of these cells has been challenging. Some types of fibroblasts support the heart’s structural integrity and maintain good blood flow through the heart’s blood vessels, while others are responsible for driving inflammation and the development of scar tissue. Only recently, with the wide availability of the most advanced single cell sequencing technologies, could scientists peg which groups of cells are which.

“These various types of fibroblasts highlight newly recognised opportunities to craft treatment strategies that specifically block the type of fibroblasts that promote scarring and protect fibroblasts that maintain the structure of the heart, so the heart doesn’t rupture,” Lavine said. “Our research suggests that the fibroblasts that promote scarring in the injured heart are very similar to fibroblasts associated with cancer and other inflammatory processes. This opens the door to immunotherapies that potentially can stop the inflammation and resulting scar tissue.”

The research team, co-led by Junedh Amrute, a graduate student in Lavine’s lab, used genetic methods to demonstrate that a signaling molecule called IL-1 beta was important in a chain of events driving fibroblasts to create scar tissue in heart failure. With that in mind, they tested a mouse monoclonal antibody that blocks IL-1 beta and found beneficial effects in the mouse hearts. The mouse monoclonal antibody was provided by Amgen, whose scientists were also co-authors of the study. Monoclonal antibodies are proteins manufactured in the lab that modulate the immune system. The treatment reduced the formation of scar tissue and improved the pumping capacity of the mouse hearts, as measured on an echocardiogram.

At least two FDA-approved monoclonal antibodies, canakinumab and rilonacept, can block IL-1 signalling. These immunotherapies are approved to treat inflammatory disorders such as juvenile idiopathic arthritis and recurrent pericarditis, which is inflammation of the sac surrounding the heart.

One of these antibodies also has been evaluated in a clinical trial for atherosclerosis, a buildup of plaque that hardens the arteries. The trial, called CANTOS (Canakinumab Anti-inflammatory Thrombosis Outcome Study), showed a benefit for study participants with atherosclerosis.

“Even though this trial was not designed to test this treatment in heart failure, there are hints in the data that the monoclonal antibody might be beneficial for patients with heart failure,” Lavine said. “Secondary analyses of the data from this trial showed that the treatment was associated with a sizable reduction in heart failure admissions compared with standard care. Our new study may help explain why.”

Even so, the IL-1 antibody used in the CANTOS study had some side effects, such as increased risk of infection, that could perhaps be reduced with a more targeted antibody that specifically blocks IL-1 signaling in cardiac fibroblasts, according to the researchers.

“We are hopeful that the combination of all of this evidence, including our work on the IL-1 beta pathway, will lead to the design of a clinical trial to specifically test the role of targeted immunotherapy in heart failure patients,” Lavine said.

Source: Washington University School of Medicine

Categories : COVID Immune SystemTags :

New Discovery Explains How SARS-CoV-2 Evades Anti-viral Immunity

On By ModernMedia
Image by Fusion Medical on Unsplash

The novel coronavirus SARS-CoV-2 has an enzyme that can counteract a cell’s innate defence mechanism against viruses, explaining why it is more infectious than the previous SARS and MERS-causing viruses. This discovery, from Kobe University, may point the way to the development of more effective drugs against this and possibly similar, future diseases.

When a virus attacks, the body’s immune response has two basic layers of defence: the innate and the adaptive immune systems. While the adaptive immune system grows stronger against a specific pathogen as the body is exposed to it multiple times and which forms the basis of vaccinations, the innate immune system is an assortment of molecular mechanisms that work against a broad range of pathogens at a basic level. The Kobe University virologist SHOJI Ikuo says, “The new coronavirus, however, is so infectious that we wondered what clever mechanisms the virus employs to evade the innate immune system so effectively.”

Shoji’s team previously worked on the immune response to hepatitis viruses and investigated the role of a molecular tag called “ISG15” the innate immune system attaches to the virus’s building blocks. Having learned that the novel coronavirus has an enzyme that is especially effective in removing this tag, he decided to use his team’s expertise to elucidate the effect of the ISG15 tag on the coronavirus and the mechanism of the virus’s countermeasures.

In a paper in the Journal of Virology, the Kobe University-led team is now the first to report that the ISG15 tag gets attached to a specific location on the virus’s nucleocapsid protein, the scaffold that packages the pathogen’s genetic material. For the virus to assemble, many copies of the nucleocapsid protein need to attach to each other, but the ISG15 tag prevents this, which is the mechanism behind the tag’s antiviral action. “However, the novel coronavirus also has an enzyme that can remove the tags from its nucleocapsid, recovering its ability to assemble new viruses and thus overcoming the innate immune response,” explains Shoji.

The novel coronavirus shares many traits with the SARS and MERS viruses, which all belong to the same family of viruses – which also have an enzyme that can remove the ISG15 tag. But their versions are less efficient at it than the one in the novel coronavirus, Shoji’s team found. And in fact, it has been reported recently that the previous viruses’ enzymes have a different primary target. “These results suggest that the novel coronavirus is simply better at evading this aspect of the innate immune system’s defence mechanism, which explains why it is so infectious,” says Shoji.

But understanding just why the novel coronavirus is so effective also points the way to developing more effective treatments. The Kobe University researcher explains: “We may be able to develop new antiviral drugs if we can inhibit the function of the viral enzyme that removes the ISG15 tag. Future therapeutic strategies may also include antiviral agents that directly target the nucleocapsid protein, or a combination of these two approaches.”

Source: Kobe University

Categories : Gender Pain ManagementTags :

Men and Women Use Different Biological Systems to Reduce Pain

On By ModernMedia
Photo by Sasun Bughdaryan on Unsplash

In a new study evaluating meditation for chronic lower back pain, researchers at University of California San Diego School of Medicine have discovered that men and women utilise different biological systems to relieve pain. While men relieve pain by releasing endogenous opioids, the body’s natural painkillers, women rely instead on other, non-opioid based pathways. The study was published in PNAS Nexus.

Synthetic opioid drugs, such as morphine and fentanyl, are the most powerful class of painkilling drugs available. Women are known to respond poorly to opioid therapies, which use synthetic opioid molecules to bind to the same receptors as naturally-occurring endogenous opioids. This aspect of opioid drugs helps explain why they are so powerful as painkillers, but also why they carry a significant risk of dependence and addiction.

“Dependence develops because people start taking more opioids when their original dosage stops working,” said Fadel Zeidan, PhD, professor of anaesthesiology and Endowed Professor in Empathy and Compassion Research at UC San Diego Sanford Institute for Empathy and Compassion. “Although speculative, our findings suggest that maybe one reason that females are more likely to become addicted to opioids is that they’re biologically less responsive to them and need to take more to experience any pain relief.”

The study combined data from two clinical trials involving a total of 98 participants, including both healthy individuals and those diagnosed with chronic lower back pain. Participants underwent a meditation training program, then practiced meditation while receiving either placebo or a high-dose of naloxone, a drug that stops both synthetic and endogenous opioids from working. At the same time, they experienced a very painful but harmless heat stimulus to the back of the leg. The researchers measured and compared how much pain relief was experienced from meditation when the opioid system was blocked versus when it was intact.

The study found:

  • Blocking the opioid system with naloxone inhibited meditation-based pain relief in men, suggesting that men rely on endogenous opioids to reduce pain.
  • Naloxone increased meditation-based pain relief in women, suggesting that women rely on non-opioid mechanisms to reduce pain.
  • In both men and women, people with chronic pain experienced more pain relief from meditation than healthy participants.

“These results underscore the need for more sex-specific pain therapies, because many of the treatments we use don’t work nearly as well for women as they do for men,” said Zeidan.

The researchers conclude that by tailoring pain treatment to an individual’s sex, it may be possible to improve patient outcomes and reduce the reliance on and misuse of opioids.

“There are clear disparities in how pain is managed between men and women, but we haven’t seen a clear biological difference in the use of their endogenous systems before now,” said Zeidan. “This study provides the first clear evidence that sex-based differences in pain processing are real and need to be taken more seriously when developing and prescribing treatment for pain.”

Source: University of California – San Diego