Tag: 23/7/24

Categories : Cardiovascular Disease Obstetrics & GynaecologyTags : Leave a comment

Women Lose More Years of Life After a Heart Attack Than Men

On By ModernMedia
Photo by Joice Kelly on Unsplash

A new study shows that women lose more years of life after a heart attack than men. A 50-year-old woman with a large heart attack loses an average of 11 years, while an 80-year-old man with a small heart attack loses an average of 5 months of life. The results of the study, led by researchers at Karolinska Institutet and Danderyd Hospital, are published in the journal Circulation.

The new study examined 335 000 individuals with first-time myocardial infarction registered in the SWEDEHEART quality registry during the period 1991-2022. The individuals with myocardial infarction were compared with 1.6 million individuals without myocardial infarction using data from Statistics Sweden and the National Board of Health and Welfare. Using the comparator population and new statistical methods, the difference in life expectancy between heart attack individuals and comparison individuals could be calculated, providing a measure of how much life expectancy was shortened due to the disease. 

“We found that there were large differences between groups. Women and young individuals lost the most life expectancy when they had a heart attack. If the cardiac function was impaired after the infarction, the effects were even greater. For example, a 50-year-old woman with impaired cardiac function loses an average of 11 years in 2022 compared to an 80-year-old man with normal cardiac function who loses an average of 5 months in life expectancy,” says first author Christian Reitan, researcher at the Department of Clinical Sciences, Danderyd Hospital, Karolinska Institut. 

Parameters affecting heart attack risk

The researchers were also able to take into account differences in income, education, other illnesses and medication at the time of the illness – which helped to measure the effect of the heart attack itself when everything else was taken into account.

“The results showed that a fairly large part of the reduction in life expectancy disappeared, that is, much of the reduction in life expectancy is explained by factors other than the heart attack itself, but which may still be associated with heart attack, such as socioeconomics or other diseases such as hypertension and diabetes. Provided that the patient had preserved cardiac function, we saw that the gender difference had disappeared. We interpret this to mean that the effect of the heart attack, and thus also the care for heart attacks, is similar between the sexes and that the large reduction in life expectancy we see in women is due to differences in risk factors, other diseases and socioeconomics,” says Christian Reitan. 

According to the researchers, there is a lack of individualized heart attack care in Sweden for women. The study shows that women who have a heart attack lose more years of life than men of the same age.

“If a woman had impaired cardiac function, the gender difference was large. We don’t have the data to answer why, but it raises questions about whether women get as good follow-up and treatment for heart failure as men, or whether it is simply a more serious condition for a woman. Our findings are important because they challenge existing guidelines for heart attack treatment today. By identifying high-risk groups, we can hopefully better tailor treatment to the individual. We believe that ‘years of life lost’ is a good and easy-to-understand measure of risk for both doctors and patients. It makes it easier for us to assess and communicate the seriousness of the disease,” concludes Christian Reitan. 

Source: Karolinska Institutet

Categories : Cancer Obstetrics & GynaecologyTags : Leave a comment

New Surgical Method for Cervical Cancer Shows Promising Results

On By ModernMedia
Cervical cancer. Credit: Scientific Animations CC4.0

A recently published study has compared a new surgical method, called cancer field surgery (Total Mesometrial Resection, TMMR), with the current standard treatment for primary management of cervical cancer.

The new TMMR method was developed over 20 years ago by Karolinska Institutet’s partners at the Leipzig University Hospital. Previous publications have suggested favourable results without the need for radiation therapy. Omitting radiation therapy could potentially improve quality of life for treated women.

In the study, the researchers demonstrate that TMMR is associated with improved oncological outcomes for early stages of cervical cancer. The data suggest that TMMR may replace current treatment strategies and radiation therapy could be spared for salvage treatment. This breakthrough motivates continued work in this field.

Research of this kind heavily relies on well-functioning collaborations with other researchers. Beyond providing essential data for the project, it also strengthens international cooperation, facilitating the dissemination of our findings. The researchers plan to further explore the potential of cancer field surgery in gynaecological cancer to establish the method in future treatment strategies.

Source: Karolinska Institutet

Categories : Regenerative MedicineTags : Leave a comment

Breakthrough in Understanding Skeletal Muscle Regeneration

On By ModernMedia
Photo by Jonathan Borba on Unsplash

Newly published research from the University of Houston College of Pharmacy identifies key mechanisms of skeletal muscle regeneration and growth of muscles following resistance exercise. The findings, published in EMBO Reports, open the door to the development of targeted therapies for various muscle disorders, like Muscular Dystrophy, which affect millions of people worldwide.

When it comes to muscles and muscle disorders, the importance of a discovery like this cannot be overstated.

Muscles’ regenerative powers

Skeletal muscles are formed during embryonic development by the fusion of hundreds of specialised cells called myoblasts. Adult skeletal muscles maintain regenerative capacity, which is attributed to the presence of muscle stem cells, named satellite cells.

After injury, satellite cells undergo several rounds of proliferation followed by their differentiation into myoblasts. These myoblasts once again fuse with each other and to injured myofibres to accomplish muscle regeneration.

In many muscular disorders, this intrinsic capacity of muscles to regenerate is diminished resulting in the loss of muscle mass and function.

Key signalling protein

UH researchers found that Inositol-requiring enzyme 1, a key signalling protein, is essential for myoblast fusion during muscle formation and growth.

“During muscle regeneration, IRE1 augments the activity of X-box binding protein 1 which in turn stimulates the gene expression of multiple transmembrane proteins required for myoblast fusion,” reports Ashok Kumar, professor of pharmacy in the Department of Pharmacological and Pharmaceutical Sciences.

According to researchers, increasing the levels of IRE1 or XBP1 in muscle stem cells outside the body, followed by their injection in patients’ muscle tissues will improve muscle repair and reduce the severity of disease.

“We also found that augmenting the levels of IRE1α or XBP1 in myoblasts leads to the formation of myotubes (muscle cells) having an increased diameter,” said Kumar.

That increase in diameter can be significant.

“Size is very important for muscle. Muscle grows only in size, not in number,” said Aniket Joshi, a graduate student in Kumar’s lab and first author on the article. “Muscular people have larger muscle cells. Larger muscles generally work better- can lift more weight, run and walk faster, and improve overall metabolism of the body and prevent various diseases, such as type II diabetes.”

Flexing their muscles

This new research is not the first flex for Kumar’s team. In 2021, research from Kumar’s lab published in the ELife journal described the role of the IRE1α/XBP1 signaling axis in regeneration of healthy skeletal muscle after acute injury and in models of Duchenne Muscular Dystrophy. In this study, they found that IRE1α/XBP1 signaling axis also plays an important cell autonomous role in satellite cells.

Source: University of Houston

Categories : CancerTags : Leave a comment

Diabetic Neuropathy Drug Reduces Drug Resistance in Lung Cancer

On By ModernMedia
In this image from a genetically engineered mouse model, lung cancer driven by the Kras oncogene shows up in purple. As a key driver in many types of cancer, the Kras gene makes a promising target for new cancer therapies. Credit: National Cancer Institute, National Institutes of Health

A medication used to treat diabetic neuropathy may enhance the effectiveness of chemotherapy for patients with lung cancer, according to new findings from the University of Missouri School of Medicine. Despite surgical and chemotherapy treatment, more than 50% of non-metastatic, non-small lung cancer patients see recurrences, in large part because of drug-resistant cancer cells. Researchers identified a way to make these cells more susceptible to chemotherapy, said Dr Jussuf Kaifi, author of the new study published in Clinical Cancer Research.

“Traditional treatments for lung cancer, including chemotherapy, often have little to no effect on the cancer because of drug resistance,” Kaifi said. “It is a major cause of mortality in patients, so finding ways to circumvent drug and chemotherapy resistance is vital to improving patient outcomes.”

The study examined 10 non-small cell lung cancer tumours, half of which were identified as drug resistant. The drug-resistant tumours showed overexpression of a certain enzyme, AKR1B10. When treated with the diabetic neuropathy medication, epalrestat, the tumours became less drug resistant, causing their sensitivity to chemotherapy to significantly increase.

Epalrestat is available in several countries (excluding South Africa) and well-tolerated by patients, but it is not yet approved for use by the Food and Drug Administration in the United States. The medication is currently in high-level clinical trials as part of the FDA’s approval process. If given FDA approval, epalrestat could be fast-tracked in the US as an anti-cancer drug for lung cancer patients.

“In general, developing new drugs for cancer treatment is an extremely lengthy, expensive and inefficient process,” Kaifi said. “In contrast, ‘repurposing’ these drugs to other diseases is much faster and cheaper. In view of overcoming drug resistance, epalrestat can rapidly be advanced to the clinic to improve cure rates in lung cancer patients.”

Source: University of Missouri

Categories : New Compounds and Treatments OphthalmologyTags : Leave a comment

Repurposed Drug Combination Promising in the Treatment of Retinal Degenerations

On By ModernMedia
Retina and nerve cells. Credit: NIH

An international team of researchers have tested a combination treatment incorporating three existing drugs and successfully slowed disease progression in pre-clinical retinopathy models. Their results, which used tamsulosin, metoprolol and bromocriptine are published in Nature Communications.

Drug repurposing refers to the use of existing drugs to treat diseases or conditions which they were not originally developed or approved for, and offer a strategy to treat rare diseases for which new drug development is too costly. The new study focused on drug repurposing in the context of inherited retinal degenerations, IRDs. IRDs are a group of genetic diseases that cause the deterioration of retinal anatomy and function, leading to gradual loss of vision and often blindness. Most IRDs are currently inaccessible therapeutically, comprising an unmet medical need for a substantial population worldwide.

A combination treatment incorporating three drugs slowed disease progression 

The researchers found that a combination treatment incorporating three drugs significantly slowed disease progression and decreased disease manifestation in four different animal models of IRD. The combination included the blood pressure and heart failure drug metoprolol, and tamsulosin, which is used for the treatment of benign prostatic hyperplasia, as well as the nowadays less commonly used Parkinson’s disease drug bromocriptine.

“In drug repurposing, it does not matter to which diseases or conditions the drugs were originally developed for, but it is the molecular-level effects of drugs, or pharmacology, that count,” says first author Dr Henri Leinonen, currently Adjunct Professor of Neuropharmacology at the University of Eastern Finland.

In retinal degenerations, intracellular secondary messengers such as cyclic adenosine monophosphate and calcium are believed to be overactive, exacerbating the disease. Metoprolol, tamsulosin and bromocriptine suppress the activity of these secondary messengers via their own distinct cell membrane-receptor actions.

“We hypothesised that the combined effect of these drugs would alleviate the disease, which it indeed did in several distinct animal models of IRDs. However, the efficacy and safety of this combination in humans with retinal degeneration is not guaranteed, and controlled clinical trials to test these are needed,” Dr Leinonen notes.

It is noteworthy that none of the drugs used in the study were effective against retinal degeneration on their own; instead, their combination was necessary for efficacy. According to Dr Leinonen, the same phenomenon may apply to many diseases that are currently untreatable, and especially in multifactorial diseases, effective treatment may require multiple drugs to be used simultaneously.

Drug repurposing could provide solutions especially for the treatment of rare diseases

Rare diseases, IRDs included, are seldom of major interest for the pharmaceutical industry due to a lack of economic incentives. But drug repurposing, actively researched in academia, is a promising method to find solutions for rare diseases that remain therapeutically inaccessible.

The most significant advantages of drug repurposing can be found in faster drug development times and lower costs. Since repurposed drugs have already undergone several mandatory safety tests and early stages of clinical trials, their market entry is considerably faster and cheaper than that of completely new drugs. Drug safety is also an important aspect, as the relative safety of repurposed drugs compared to a completely new chemical reduces risks and uncertainty, which is often considered the most critical point in the drug development process.

Source: University of Finland