Month: February 2024

Categories : Lab Tests and ImagingTags :

Experimental Model Identifies New Drug–drug Interactions

On By ModernMedia
Photo by Myriam Zilles on Unsplash

When taking oral drugs, transporter proteins found on cells that line the gastrointestinal tract facilitate their entry into the bloodstream. But for many drugs, it is not known which of those transporters they use to exit the digestive tract.

Identifying the transporters used by specific drugs could help to improve patient treatment because if two drugs rely on the same transporter, they can interfere with each other and should not be prescribed together.

Researchers at MIT, Brigham and Women’s Hospital, and Duke University have developed a multipronged strategy to identify the transporters used by different drugs, which appears in Nature Biomedical Engineering. Their approach, which makes use of both tissue models and machine-learning algorithms, has already revealed that a commonly prescribed antibiotic and a blood thinner can interfere with each other.

“One of the challenges in modelling absorption is that drugs are subject to different transporters. This study is all about how we can model those interactions, which could help us make drugs safer and more efficacious, and predict potential toxicities that may have been difficult to predict until now,” says Giovanni Traverso, an associate professor of mechanical engineering at MIT, a gastroenterologist at Brigham and Women’s Hospital, and the senior author of the study.

Learning more about which transporters help drugs pass through the digestive tract could also help drug developers improve the absorbability of new drugs by adding excipients that enhance their interactions with transporters.

Former MIT postdocs Yunhua Shi and Daniel Reker are the lead authors of the study.

Drug transport

Previous studies have identified several transporters in the GI tract that help drugs pass through the intestinal lining. Three of the most commonly used, which were the focus of the new study, are BCRP, MRP2, and PgP.

For this study, Traverso and his colleagues adapted a tissue model they had developed in 2020 to measure a given drug’s absorbability. This experimental setup, based on pig intestinal tissue grown in the laboratory, can be used to systematically expose tissue to different drug formulations and measure how well they are absorbed.

To study the role of individual transporters within the tissue, the researchers used short strands of RNA called siRNA to knock down the expression of each transporter. In each section of tissue, they knocked down different combinations of transporters, which enabled them to study how each transporter interacts with many different drugs.

“There are a few roads that drugs can take through tissue, but you don’t know which road. We can close the roads separately to figure out, if we close this road, does the drug still go through? If the answer is yes, then it’s not using that road,” Traverso says.

The researchers tested 23 commonly used drugs using this system, allowing them to identify transporters used by each of those drugs. Then, they trained a machine-learning model on that data, as well as data from several drug databases. The model learned to make predictions of which drugs would interact with which transporters, based on similarities between the chemical structures of the drugs.

Using this model, the researchers analysed a new set of 28 currently used drugs, as well as 1595 experimental drugs. This screen yielded nearly 2 million predictions of potential drug interactions. Among them was the prediction that doxycycline, an antibiotic, could interact with warfarin, a commonly prescribed blood-thinner. Doxycycline was also predicted to interact with digoxin, which is used to treat heart failure, levetiracetam, an antiseizure medication, and tacrolimus, an immunosuppressant.

Identifying interactions

To test those predictions, the researchers looked at data from about 50 patients who had been taking one of those three drugs when they were prescribed doxycycline. This data, which came from a patient database at Massachusetts General Hospital and Brigham and Women’s Hospital, showed that when doxycycline was given to patients already taking warfarin, the level of warfarin in the patients’ bloodstream went up, then went back down again after they stopped taking doxycycline.

That data also confirmed the model’s predictions that the absorption of doxycycline is affected by digoxin, levetiracetam, and tacrolimus. Only one of those drugs, tacrolimus, had been previously suspected to interact with doxycycline.

“These are drugs that are commonly used, and we are the first to predict this interaction using this accelerated in silico and in vitro model,” Traverso says. “This kind of approach gives you the ability to understand the potential safety implications of giving these drugs together.”

Source: Massachusetts Institute of Technology

Categories : Cardiovascular DiseaseTags :

Common Hair Loss and Prostate Drug may also Cut Cardiovascular Risk

On By ModernMedia
Photo by Brett Sayles on Unsplash

The drug finasteride, also known as Propecia or Proscar, treats male pattern baldness and enlarged prostate in millions of men worldwide. But a new study published in the Journal of Lipid Research suggests that the drug may also possess a surprising, life-saving benefit: lowering cholesterol and reducing the overall risk of cardiovascular disease.

The study, led by University of Illinois Urbana-Champaign, found significant correlations between finasteride use and lower cholesterol levels in men taking part in the National Health and Nutrition Examination Survey between 2009 and 2016. In mice taking high finasteride doses, the researchers found reductions in total plasma cholesterol, delayed atherosclerosis progression, lower inflammation in the liver, and related benefits.

“When we looked at the men taking finasteride in the survey, their cholesterol levels averaged 30 points lower than men not taking the drug. I thought we’d see the opposite pattern, so it was very interesting,” said lead study author Jaume Amengual, assistant professor at U. of I.

As exciting as the survey results were, they had their limitations. Of nearly 4800 survey respondents meeting general health criteria for inclusion in the analysis, only 155, all men over 50, reported using finasteride. And the researchers couldn’t tell how much or how long men in the survey had taken the drug.

“This was not a clinical study in which you can control everything perfectly,” Amengual said. “It was more of an observation that led us to say, ‘Okay, now we’ve seen this in people. Let’s see what happens in mice.'”

But first, why would a hair loss and prostate drug affect cholesterol? Amengual studies atherosclerosis, the condition in which cholesterol plaques choke arteries, leading to stroke, heart attack, and other forms of cardiovascular disease. Because the disease is far more common in men than premenopausal women, scientists have long suspected the sex hormone testosterone is important in atherosclerosis, though its role isn’t entirely clear.

Finasteride works by blocking a protein found in hair follicles and the prostate gland that activates testosterone. The common thread, testosterone, was enough to pique Amengual’s interest.

“I was reading about this medication one day, and I started to notice that there were not many long-term studies of the implications of the drug. Initially, it was just my own curiosity, based on the fact that hormone levels are known to have an effect on atherosclerosis, hair loss, and prostate issues,” he said. “So, we decided to dig into it.”

After documenting the first-ever link, albeit observational, between finasteride and lower cholesterol in men, Amengual got doctoral student Donald Molina Chaves to see if the pattern held in mice.

Molina Chaves tested four levels of finasteride – 0, 10, 100, and 1000 mg/kg of food – in male mice genetically predisposed to atherosclerosis. The mice consumed the drug, along with a high-fat, high-cholesterol “Western” diet, for 12 weeks. After the experiment, Molina Chaves analysed the levels of cholesterol and other lipids in the mice, along with evidence of atherosclerotic plaques. He also tested gene expression in the liver, looked at bile acid metabolism, and analysed steroids, triglycerides, immune activity, and more.

“Mice that were given a high dose of finasteride showed lower cholesterol levels within the plasma as well as in the arteries,” Molina Chaves said. “There were also fewer lipids and inflammatory markers in the liver.”

Although the effects were only significant at the highest dose, a level Amengual calls outrageous for humans, he explains that mice metabolise finasteride differently than people.

“It’s an incredibly high level of the drug. But we use mice as a model, and they are extremely resistant to things that would kill any of us,” he said. “So it is not that crazy when you think about it that way.”

Humans take 1mg or 5mg doses of finasteride daily for hair loss and enlarged prostate, respectively. The fact that a clear pattern showed up in a survey of men likely taking one of these doses suggests the drug may be lowering cholesterol without the megadoses tested in mice.

The next step is for physicians to start tracking cholesterol in finasteride patients or conduct a clinical trial to verify the effect. Amengual says it may be especially important to understand how finasteride affects trans individuals.

“Over the past decade, doctors have started prescribing this drug for individuals transitioning either from male to female or female to male. In both cases, the hormonal changes can trigger hair loss,” he said. “The interesting thing is that transgender people are also at a higher risk of cardiovascular diseases. So this drug could have a potential beneficial effect to prevent cardiovascular disease not only in cis men, but also in transgender individuals.”

Finally, Amengual notes, like any medication, finasteride is not without risk. People should consult their doctors to learn more.

Source: University of Illinois College of Agricultural, Consumer and Environmental Sciences

Categories : Diet and NutritionTags :

Are Ultra-processed Foods the New ‘Silent Killer’?

On By ModernMedia
Photo by Patrick Fore on Unsplash

Nowadays, ultra-processed foods are packed with a bewildering range of additives: there are common ones like oil, fat, and sugar. There are also emulsifiers such as carrageenan, mono- and diglycerides, carboxymethylcellulose, polysorbate and soy lecithin. These continue to strip food of healthy nutrients while introducing other ingredients that could also be detrimental to human health.

Hundreds of novel ingredients never encountered by human physiology are now found in nearly 60% of the average adult’s diet and nearly 70% of children’s diets in the United States.

While obesity and lack of physical activity are well recognised contributors to avoidable morbidity and mortality, another emerging hazard is the unprecedented consumption of these ultra-processed foods in the standard American diet. This may be the new “silent” killer, as was unrecognised hypertension in previous decades.

Physicians from Florida Atlantic University’s Schmidt College of Medicine explored this hypothesis and provide important insights to health care providers in a battle where the entertainment industry, the food industry and public policy do not align with their patients’ needs. Their findings are published in a commentary in The American Journal of Medicine.

First generation of doctors to see a reduction in life expectancy

“Those of us practicing medicine in the US today find ourselves in an ignominious and unique position – we are the first cohort of health care professionals to have presided over a decline in life expectancy in 100 years,” said Dawn H. Sherling, MD, corresponding author, associate program director for the internal medicine residency and an associate professor of medicine, FAU Schmidt College of Medicine. “Our life expectancy is lower than other economically comparable countries. When we look at increasing rates of non-communicable diseases in less developed nations, we can see a tracking of this increase along with increasing consumption of ultra-processed foods in their diets.”

Although professional organizations such as the American College of Cardiology cautions patients to “choose minimally processed foods instead of ultra-processed foods” in their 2021 dietary guidelines, there is a caveat that “there is no commonly accepted definition for ultra-processed foods, and some healthy foods may exist within the ultra-processed food category.”

“When the components of a food are contained within a natural, whole food matrix, they are digested more slowly and more inefficiently, resulting in less calorie extraction, lower glycaemic loads in general, and lower rise in triglyceride-rich lipoproteins after eating, which could result in atherosclerotic plaque,” said Allison H. Ferris, MD, senior author, an associate professor and chair, Department of Medicine, and director of the internal medicine residency program, FAU Schmidt College of Medicine. “Therefore, even if the troublesome additives were removed from the ultra-processed food, there would still be concern for an over-consumption of these products possibly leading to obesity, diabetes and heart disease.”

The authors add that public health organisations are increasingly making use of the NOVA classification system, which divides foods into four categories – whole foods, culinary ingredients (items like butter, oil and salt), traditionally processed foods (such as bread and yogurt made with few ingredients), and ultra-processed foods – or those foods that are industrially made and use ingredients not normally found in a domestic kitchen.

According to the authors, one plausible mechanism to explain the hazards is that ultra-processed foods contain emulsifiers and other additives that the mammalian gastrointestinal tract mostly does not digest. They may act as a food source for our microbiota, and as such may be creating a dysbiotic microbiome that can, in the right host, promote disease.

“Additives, such as maltodextrin, may promote a mucous layer that is friendly to certain species of bacteria that are found in greater abundance in patients with inflammatory bowel disease,” said Sherling. “When the mucous layer is not properly maintained, the epithelial cell layer may become vulnerable to injury, as has been shown in feeding studies using carrageenan in humans and other studies in mice models, using polysorbate-80 and cellulose gum, triggering immunologic responses in the host.”

Food companies as powerful as the 20th century’s tobacco companies

The authors add that there have been marked increases in colorectal cancer in the US, especially among younger adults. They opine that increased ultra-processed food consumption may be a contributor as well as to several other gastrointestinal diseases.

“Whether ultra-processed foods contribute to our currently rising rates of non-communicable disease requires direct testing in analytic studies designed a priori to do so,” said Charles H. Hennekens, MD, FACPM, co-author, the First Sir Richard Doll Professor of Medicine and senior academic advisor, FAU Schmidt College of Medicine. “In the meantime, we believe it is incumbent upon all health care professionals to discuss the benefits of increasing consumption of whole foods and reducing consumption of ultra-processed foods with their patients.”

The authors also opine that just as the dangers of tobacco began to emerge during the middle of the prior century, decades passed before the preponderance of the evidence and the efforts of forward-thinking health officials prompted policy change to discourage the use of cigarettes. They say there is likely to be a similar path for ultra-processed foods.

“The multinational companies that produce ultra-processed foods are just as, if not more, powerful than tobacco companies were in the last century, and it is unlikely that governments will be able to move quickly on policies that will promote whole foods and discourage the consumption of ultra-processed foods,” said Sherling. “Importantly, health care providers also should remain cognizant of the difficulties that many of our patients have in being able to afford and find healthier options, which calls for a broader public health response.”

Source: Florida Atlantic University

Categories : Cardiovascular DiseaseTags :

High Levels of Niacin Linked to Cardiovascular Disease

On By ModernMedia
Photo by Robina Weermeijer on Unsplash

Cleveland Clinic researchers have identified a new pathway that contributes to cardiovascular disease associated with high levels of niacin, a common B vitamin previously recommended to lower cholesterol.

The team, led by Stanley Hazen, MD, PhD, reported in Nature Medicine that they had found a link between 4PY, a breakdown product from excess niacin, and cardiovascular disease. Higher circulating levels of 4PY were strongly associated with development of heart attack, stroke and other adverse cardiac events in large-scale clinical studies.

The researchers also showed in preclinical studies that 4PY directly triggers vascular inflammation which damages blood vessels and can lead to atherosclerosis over time. The study also details genetic links between 4PY and vascular inflammation.

The findings provide a foundation for potential new interventions and therapeutics to reduce or prevent that inflammation.

“What’s exciting about these results is that this pathway appears to be a previously unrecognised yet significant contributor to the development of cardiovascular disease,” said Dr Hazen, Chair of Cardiovascular and Metabolic Sciences at Cleveland Clinic’s Lerner Research Institute and Co-Section Head of Preventive Cardiology in the Heart, Vascular & Thoracic Institute.

“What’s more, we can measure it, meaning there is potential for diagnostic testing. These insights set the stage for developing new approaches to counteract the effects of this pathway.”

Niacin (vitamin B-3) is very common in a Western diet. “For decades, the United States and more than 50 nations have mandated niacin fortification in staple foods such as flour, cereals and oats to prevent disease related to nutritional deficiency,” said Dr Hazen.

Yet one in four subjects in the researchers’ patient cohorts appear to be getting too much, and had high levels of 4PY, which appears to contribute to cardiovascular disease development.

Dr. Hazen compares our intake of niacin as multiple taps pouring water into a bucket.

Once that bucket is filled, it begins to spill over. The human body then needs to process that spill-over and produce other metabolites, including 4PY.

“The main takeaway is not that we should cut out our entire intake of niacin – that’s not a realistic approach,” said Dr Hazen.

“Given these findings, a discussion over whether a continued mandate of flour and cereal fortification with niacin in the US could be warranted.”

Dr. Hazen notes broader use of over-the-counter supplements made with different forms of niacin have also become popular because of presumed anti-aging purposes.

He adds that patients should consult with their doctors before taking over-the-counter supplements and focus on a diet rich in fruit and vegetables while avoiding excess carbohydrates.

The new findings also might help explain why niacin, one of the first treatments prescribed to lower LDL cholesterol, is no longer a go-to treatment for for this.

Eventually niacin was shown to be less effective than other cholesterol-lowering drugs and was associated with other negative effects and higher mortality rates in previous research.

“Niacin’s effects have always been somewhat of a paradox,” Dr Hazen said.

“Despite niacin lowering of cholesterol, the clinical benefits have always been less than anticipated based on the degree of LDL reduction. This led to the idea that excess niacin caused unclear adverse effects that partially counteracted the benefits of LDL lowering. We believe our findings help explain this paradox. This illustrates why investigating residual cardiovascular risk is so critical; we learn so much more than what we set out to find.”

The study authors note that long-term investigations are needed to assess the effect of chronic elevation of 4PY levels on atherosclerosis and other phenotypes.

Source: Cleveland Clinic

Categories : Mental Health Obstetrics & GynaecologyTags :

Antidepressants Impact Prefrontal Cortex Development

On By ModernMedia
Photo by William Fortunato on Pexels

A new study published in Nature Communications suggests that use of antidepressants can impact early post-natal brain development, potentially contributing to the development of mental health disorders. The study, led by researchers at the University of Colorado Anschutz Medical Campus, focused on the effect of fluoxetine, commonly used in medications such as Prozac and Sarafem for treating depression and perinatal depression, on the developing prefrontal cortex of mice.

Since fluoxetine works by increasing the levels of serotonin in the brain, the researchers looked at the impact serotonin has on prefrontal cortex development.

“While it is known that serotonin plays a role in the brain development, the mechanisms responsible for this influence, specifically in the prefrontal cortex, have been unclear, ” said lead author Won Chan Oh, PhD, assistant professor in the Department of Pharmacology at CU Anschutz.

Changes in gestational and early postnatal serotonin levels can arise from many causes including maternal deprivation or abuse, diets high or low in tryptophan, or the use of medications such as selective serotonin reuptake inhibitors (SSRIs) that can readily cross the placenta or be passed to offspring through breast feeding. Disbalances of 5-HT during brain development are associated with increased risk of neurodevelopmental disorders such as autism spectrum disorder and long-lasting behavioural deficits, but the underlying mechanisms remain elusive.

Oh and his student, Roberto Ogelman, a neuroscience PhD candidate, found serotonin directly influences nascent and immature excitatory synaptic connections in the prefrontal cortex, which if disrupted or dysregulated during early development can contribute to various mental health disorders.

“Our research uncovers the specific processes at the synaptic level that explain how serotonin contributes to the development of this important brain region during early-life fluoxetine exposure,” adds Oh. “We are the first to provide experimental evidence of the direct impact of serotonin on the developing prefrontal cortex in mice.”

To study the effect, the researchers looked at the impact of deficiency and surplus of serotonin on brain development in mice. They discovered that serotonin is not just involved in overall brain function but also has a specific role in influencing how individual connections between neurons change and adapt, contributing to the brain’s ability to learn and adjust.

“Understanding this correlation has the potential to help with early intervention and the development of new therapeutics for neurodevelopmental disorders involving serotonin dysregulation,” said Oh.

The researchers plan to continue studying the impact of fluoxetine, next examining its impact on a developing brain later in life.

Source: Colorado University Anschutz Medical Campus

Categories : Uncategorized

Fasting-mimicking Diets Reduce Signs of Biological Ageing

On By ModernMedia
Photo by Pixabay: https://www.pexels.com/photo/broccoli-161514/

Cycles of a diet that mimics fasting can reduce signs of immune system ageing, as well as insulin resistance and liver fat in humans, resulting in a lower biological age, according to a new study in Nature Communications. The USC Leonard Davis School of Gerontology-led study adds to the body of evidence supporting the beneficial effects of the fasting-mimicking diet (FMD).

The FMD is a five-day diet high in unsaturated fats and low in overall calories, protein, and carbohydrates and is designed to mimic the effects of a water-only fast while still providing necessary nutrients and making it much easier for people to complete the fast.

The diet was developed by the laboratory of USC Leonard Davis School Professor Valter Longo, the senior author of the new study.

“This is the first study to show that a food-based intervention that does not require chronic dietary or other lifestyle changes can make people biologically younger, based on both changes in risk factors for aging and disease and on a validated method developed by the Levine group to assess biological age,” Longo said.

Previous research led by Longo has indicated that brief, periodic FMD cycles are associated with a range of beneficial effects, including: promoting stem cell regeneration, lessening chemotherapy side effects, and reducing the signs of dementia in mice. In addition, the FMD cycles can lower the risk factors for cancer, diabetes, heart disease and other age-related diseases in humans.

The Longo lab also had previously shown that one or two cycles of the FMD for five days a month increased the healthspan and lifespan of mice on either a normal or Western diet, but the effects of the FMD on aging and biological age, liver fat, and immune system aging in humans were unknown until now.

Lower disease risks & more youthful cells

The study analysed the diet’s effects in two clinical trial populations, each with men and women between the ages of 18 and 70. Patients randomised to the fasting-mimicking diet underwent 3-4 monthly cycles, adhering to the FMD for 5 days, then ate a normal diet for 25 days.

The FMD is comprised of plant-based soups, energy bars, energy drinks, chip snacks, and tea portioned out for 5 days as well as a supplement providing high levels of minerals, vitamins, and essential fatty acids.

Patients in the control groups were instructed to eat either a normal or Mediterranean-style diet.

An analysis of blood samples from trial participants showed that patients in the FMD group had lower diabetes risk factors, including less insulin resistance and lower HbA1c results.

Magnetic resonance imaging also revealed a decrease in abdominal fat as well as fat within the liver, improvements associated with a reduced risk of metabolic syndrome.

In addition, the FMD cycles appeared to increase the lymphoid-to-myeloid ratio – an indicator of a more youthful immune system.

Further statistical analysis of the results from both clinical studies showed that FMD participants had reduced their biological age, a measure of how well one’s cells and tissues are functioning, by 2.5 years on average.

“This study shows for the first time evidence for biological age reduction from two different clinical trials, accompanied by evidence of rejuvenation of metabolic and immune function,” Longo said.

The study, conducted by first authors Sebastian Brandhorst, USC Leonard Davis research associate professor, and Morgan E. Levine, founding principal investigator of Altos Labs and USC Leonard Davis PhD alumna, lends more support to the FMD’s potential as a short-term periodic, achievable dietary intervention that can help people lessen their disease risk and improve their health without extensive lifestyle changes, Longo said.

“Although many doctors are already recommending the FMD in the United States and Europe, these findings should encourage many more healthcare professionals to recommend FMD cycles to patients with higher than desired levels of disease risk factors as well as to the general population that may be interested in increased function and younger age,” Longo said.

Source: University of Southern California

Categories : Cardiovascular Disease Diet and NutritionTags :

Excessive Protein Consumption Increases Atherosclerosis Risk

On By ModernMedia

Cardiovascular pitfalls to increasing protein intake discovered

Image by Scientific Animations, CC4.0

University of Pittsburgh School of Medicine researchers discovered a molecular mechanism by which excessive dietary protein could increase atherosclerosis risk. The study, published in Nature Metabolism, combined small human trials with in vitro human and mouse cell experiments.

It showed that consuming over 22% of dietary calories from protein can lead to increased activation of immune cells that play a role in atherosclerotic plaque formation, driving the disease risk.

Furthermore, the scientists showed that one amino acid, leucine, seems to have a disproportionate role in driving the pathological pathways linked to atherosclerosis, or stiff, hardened arteries.

“Our study shows that dialling up your protein intake in pursuit of better metabolic health is not a panacea. You could be doing real damage to your arteries,” said senior and co-corresponding author Babak Razani, MD, PhD, professor of cardiology at Pitt.

“Our hope is that this research starts a conversation about ways of modifying diets in a precise manner that can influence body function at a molecular level and dampen disease risks.”

According to a survey of an average American diet over the last decade, Americans generally consume a lot of protein, mostly from animal sources.

Further, nearly a quarter of the population receives over 22% of all daily calories from protein alone.

That trend is likely driven by the popular idea that dietary protein is essential to healthy living, says Razani.

But his and other groups have shown that overreliance on protein may not be such a good thing for long-term health.

Following their 2020 research, in which Razani’s laboratory first showed that excess dietary protein increases atherosclerosis risk in mice, his next study in collaboration with Bettina Mittendorfer, PhD, a metabolism expert at the University of Missouri, Columbia, delved deeper into the potential mechanism and its relevance to the human body.

To arrive at the answer, Razani’s laboratory, led by first-authors Xiangyu Zhang, Ph.D., and Divya Kapoor, M.D., teamed up with Mittendorfer’s group to combine their expertise in cellular biology and metabolism and perform a series of experiments across various models, from cells to mice to humans.

“We have shown in our mechanistic studies that amino acids, which are really the building blocks of the protein, can trigger disease through specific signaling mechanisms and then also alter the metabolism of these cells,” Mittendorfer said.

“For instance, small immune cells in the vasculature called macrophages can trigger the development of atherosclerosis.”

Based on initial experiments in healthy human subjects to determine the timeline of immune cell activation following ingestion of protein-enriched meals, the researchers simulated similar conditions in mice and in human macrophages, immune cells that are shown to be particularly sensitive to amino acids derived from protein.

Their work showed that consuming more than 22% of daily dietary calories through protein can negatively affect macrophages that are responsible for clearing out cellular debris, leading to the accumulation of a “graveyard” of those cells inside the vessel walls and worsening of atherosclerotic plaques overtime.

Interestingly, the analysis of circulating amino acids showed that leucine, an amino acid enriched in animal-derived foods like beef, eggs and milk, is primarily responsible for abnormal macrophage activation and atherosclerosis risk, suggesting a potential avenue for further research on personalized diet modification, or “precision nutrition.”

Razani is careful to note that many questions remain to be answered, mainly: What happens when a person consumes between 15% of daily calories from protein as recommended by the USDA and 22% of daily calories from protein, and if there is a ‘sweet spot’ for maximising the benefits of protein (such as muscle gain) while avoiding kick-starting a molecular cascade of damaging events leading to cardiovascular disease.

The findings are particularly relevant in hospital settings, where nutritionists often recommend protein-rich foods for the sickest patients to preserve muscle mass and strength.

“Perhaps blindly increasing protein load is wrong,” Razani said.

“Instead, it’s important to look at the diet as a whole and suggest balanced meals that won’t inadvertently exacerbate cardiovascular conditions, especially in people at risk of heart disease and vessel disorders.”

Razani also notes that these findings suggest differences in leucine levels between diets enriched in plant and animal protein might explain the differences in their effect on cardiovascular and metabolic health.

“The potential for this type of mechanistic research to inform future dietary guidelines is quite exciting,” he said.

Source: University of Pittsburgh

Categories : Pain ManagementTags :

Can Yoga Effectively Treat Chronic Back Pain?

On By ModernMedia
Photo by Sasun Bughdaryan on Unsplash

New research published in the Journal of Orthopaedic Research suggests that the physical postures, breathing exercises, and mindfulness practices of yoga may benefit individuals with back pain.

In the study, 10 women with and 11 without chronic low back pain underwent an 8‐session yoga program over 4 weeks, with the first session conducted in a clinic and the rest delivered with a tele‐approach. Women with chronic low back pain experienced a significant decrease in pain intensity, as assessed through a 10-point visual analogue scale (an average pain of 6.80 at the start, dropped to 3.30 after the sessions) and through a spine-related measure called the flexion–relaxation phenomenon, which is often absent or disrupted in people with low back pain  (5.12 at the start versus 9.49 after the sessions).

The findings suggest yoga can positively impact the neuromuscular response during trunk flexion and pain perception in individuals with chronic low back pain.

“It was interesting to show the role that yoga might play in the management of chronic back pain,” said corresponding author Prof Alessandro de Sire, MD, of the University of Catanzaro “Magna Graecia” and University Hospital “Renato Dulbecco,” in Italy.

The authors noted that further research is warranted to assess yoga’s long‐term effects.

Source: Wiley

Categories : HIV Medical IndustryTags :

First HIV Antiretrovirals Manufactured in Space Delivered Back to Earth

On By ModernMedia

For the first time, unique commercial pharmaceuticals produced using the zero gravity of outer space have been returned to Earth. After being stuck in space waiting for clearance to land, a capsule containing the small but extremely valuable cargo of HIV antiretrovirals landed in the desert in the US state of Utah. Drugs produced this way have higher purity and often improved pharmacokinetics, but have been too costly to produce until now.

In June 2023, a miniature pharmaceuticals factory built by Varda Space Industries was launched into Earth orbit. This small space startup company had only been around since 2020 – and the COVID pandemic had inspired them to look for a way to use the unique properties of space to directly benefit the health of people on Earth.

Zero gravity process can give drugs new properties

According to Varda co-founder Delian Asparouhov, gravity has significant effects somewhere between the microscopic scale and the atomic scale. This has beneficial applications in all manner of processes like crystal formation in drug manufacturing. For example, it is possible to give certain solid state pharmaceuticals improved solubility, turning a four-hour intravenous infusion into a couple of subcutaneous injections. The number of oral pills required for a treatment could be reduced. Since treatment compliance is a major obstacle to treatment, such improved drugs could significantly improve outcomes.

There are many drugs that were abandoned simply because administration was too impractical. Zero gravity manufacturing could open up these libraries of discarded drugs, Asparouhov says. It could also be possible to modify certain drugs to cross the blood–brain barrier.

Antiviral Drug Polarized crystals (photographed through a microscope) of the drug 2-3 dideoxyadenosine, also known as ddA, a drug that is closely related to AZT or azidothymidine. The antiviral effect of ddA against HIV was discovered at the National Cancer Institute. Credit: Larry Ostby (Photographer), National Cancer Institute, National Institutes of Health

Onboard the small space factory is a pharmaceutical manufacturing system designed to produce ritonavir, an antiretroviral which was initially used to treat HIV. This early antiretroviral has a number of notorious gastrointestinal and metabolic side effects. In 1998, there was a major production crisis when it was discovered that were production defects in the the oral form stemming from crystallisation problems.

Nowadays, ritonavir has been surpassed by newer antiretroviral drugs for the treatment of HIV but has been investigated for cancer treatment and during the pandemic received emergency use authorisation for COVID treatment. The samples retrieved from the capsule will only be used for evaluation purposes, to help inform the production of other pharmaceuticals.

Producing drug proteins in space is nothing new. This has been done on space stations for decades – however, these were for research purposes in developing drugs and understanding biological processes. It is only now that technology has advanced to the point where it has become cheap enough to use the unique environment of outer space to manufacture high-value products.

The capsule with its onboard factory is specially designed to be recovered and reused to minimise costs. This has only been possible thanks to rockets becoming vastly cheaper. NASA’s space shuttle cost US$65 400 for each kilogram of cargo launched into space. Today, SpaceX’s Falcon 9 rocket costs a mere 4% of that, with costs set to fall further.

Such breakneck technological development was bound to run into a snag – this one consisting of red tape. The agency that regulates commercial air and spaceflight, the Federal Aviation Administration (FAA) gave Varda a licence for their payload to be launched, but not for the capsule to re-enter the atmosphere. The vast majority of satellites don’t have to worry about that, simply burning up in the atmosphere when they can no longer function. The FAA is obviously concerned about a large module returning intact but out of control.

Eventually, after more than six months of delays and looking at alternatives such as landing in Australia instead, Varda was able to secure a re-entry permit for 21st February and its capsule returned to Earth under a parachute in the Utah desert.

Asparouhov envisions a time when much larger orbital factories produce pharmaceuticals and other valuable materials in orbit.

Categories : Cardiovascular DiseaseTags :

Raised Blood Pressure is the Leading Risk Factor for Death in Australia

On By ModernMedia

Hypertension has contributed at least 44% to CVD deaths over thirty years, more than dietary factors and tobacco

Raised blood pressure has been the leading risk factor for death in Australia for the past three decades, according to a study published February 21, 2024, in the open-access journal PLOS ONE led by Alta Schutte and Xiaoyue Xu from The George Institute for Global Health and UNSW, Sydney, with colleagues across Australia. It is also the main contributor to deaths from cardiovascular disease (CVD) specifically.

Raised blood pressure has long been recognized as a contributing factor to CVD and death, but is not always prioritized in national health plans. In this study, researchers focused on Australia, which lags behind other high-income countries in hypertension control. Data on how raised blood pressure compares to other risk factors for CVD burden – and how this changes over time – can help to guide public health agendas and inform the effectiveness of public health policies.

Researchers analysed epidemiologic data from the Global Burden of Disease (GBD) study between 1990 and 2019 to determine the leading risk factors associated with both all-cause and CVD deaths, over time and between gender and age groups. The GBD study provides data on nearly 400 diseases and 87 risk factors across 204 countries.

They found that while the contribution of raised blood pressure to these outcomes declined early in the study period (from around 54% to around 44%), it persisted as the leading risk factor for all-cause and CVD deaths. Dietary factors and tobacco use rounded out the top three risk factors. These findings strongly align with the recently established National Hypertension Taskforce of Australia, which aims to improve Australia’s blood pressure control rates from 32% to 70% by 2030 (Hypertension – Australian Cardiovascular Alliance [ozheart.org]). The research findings further advocate for the prioritisation of blood pressure control on the public health agenda.

Differences by gender and age were also seen. For example, the contribution of raised blood pressure to stroke-related deaths in males aged 25–49 years were higher than other age groups, exceeding 60% and increasing steeply over time.

The study reinforces the importance of blood pressure control and awareness. The researchers hope that the data will urge policymakers to prioritise blood pressure control efforts in Australia and will provide insight into age groups and populations that would benefit from more targeted action.

The authors add: “There is no doubt that raised blood pressure has remained the leading risk factor for all-cause and cardiovascular deaths in Australia across the past three decades. Our findings support actions to strengthen primary care and to improve the prevention, detection, treatment and control of raised blood pressure, with the goal of significantly reducing all-cause and cardiovascular deaths in Australia over the next decade.”