Day: April 11, 2022

More Evidence Linking Erectile Dysfunction Drugs to Eye Conditions

Photo by Mike Dorner on Unsplash

The risk of developing one of three serious eye conditions increases by 85 percent for regular users of common erectile dysfunction (ED) medications such as the phosphodiesterase 5 (PDE5) inhibitors, sildenafil, tadalafil, vardenafil and avanafil, according to new research.

Previously, two of the three conditions had been linked to ED medications only by anecdotal case studies. Now, these links have been confirmed for the first time by a large, epidemiological study, which appears in JAMA Ophthalmology.

“These are rare conditions, and the risk of developing one remains very low for any individual user. However, the sheer number of prescriptions dispensed each month in the US – about 20 million – means that a significant number of people could be impacted,” said first author Dr Mahyar Etminan. “Regular users of these drugs who find any changes in their vision should take it seriously and seek medical attention.”

The researchers analysed health insurance claim records of 213 000 men in the US without a history of these eye problems in the year before they became regular users of ED medications.

They followed the records to see how many men developed one or more of the three conditions, and how that rate compared to men who didn’t use the medications. After accounting for conditions associated with eye problems, such as hypertension, diabetes and coronary artery disease, they found the increased risk for each to be as follows:

A key limitation was that the study could only show correlation between eye conditions and use of these drugs, and could not prove causation. However, possible explanations can be found in the way ED medications function.

“These medications address erectile dysfunction by improving blood flow, but we know that they can also hinder blood flow in other parts of the body,” explained Dr Etminan. “So although our study doesn’t prove cause-and-effect, there is a mechanism by which these medications could conceivably lead to these problems. The totality of the evidence points toward a strong link.”

The potential risk of SRD and RVO is not covered in the information currently provided to patients along with their ED medications, unlike the ION risk which has been demonstrated by previous research.

Dr Etminan hopes his team’s work will change that. Patients who are unaware of all potential side effects might not seek help in time to avoid serious visual consequences.

Source: University of British Columbia

Unlikely Allies: Bacteria can Promote Cancer Metastasis

Scanning Electron Micrograph of a breast cancer cell. Credit: NIH

Researchers have found that bacteria lurking inside tumours promote cancer metastasis. They do so by enhancing the strength of host cells against mechanical stress in the bloodstream, promoting cell survival during tumour progression, researchers report in the journal Cell.

“Our study reveals that the cancer cell’s behaviour is also controlled by the microbes hiding inside tumours, the majority of which were originally thought to be sterile,” said senior author Shang Cai of the Westlake Laboratory of Life Sciences and Biomedicine. “This microbial involvement is distinct from the genetic, epigenetic, and metabolic components that most cancer drugs target.”

“However, our study does not mean that using antibiotics during cancer treatment will benefit patients,” he cautioned. “Therefore, it is still an important scientific question of how to manage the intratumor bacteria to improve cancer treatment in the future.”

It is known that microbes play a critical role in affecting cancer susceptibility and tumour progression, particularly in colorectal cancers. New evidence suggests however that, in a broad range of cancer types, they also form integral components of the tumour tissue itself, such as pancreatic cancer, lung cancer, and breast cancer. Microbial features are linked to cancer risk, prognosis, and treatment responses, yet the biological functions of tumour-resident microbes in tumour progression remain unclear.

Whether these microbes are actually drivers of tumour progression has been an intriguing question. “Tumour cells hijacked by microbes could be more common than previously thought, which underscores the broad clinical value of understanding the exact role of the tumour-resident microbial community in cancer progression,” Cai explained.

To find answers, Cai’s team utilised a mouse model of breast cancer with significant amounts of bacteria inside cells, similar to human breast cancer. The bacteria were found to be capable of travelling through the circulatory system with the cancer cells, playing critical roles in tumour metastasis. These passenger bacteria have the capacity to modulate the cellular actin network, promoting cell survival against mechanical stress in circulation.

“We were surprised initially at the fact that such a low abundance of bacteria could exert such a crucial role in cancer metastasis. What is even more astonishing is that only one shot of bacteria injection into the breast tumour can cause a tumour that originally rarely metastasises to start to metastasise,” Cai said. “Intracellular microbiota could be a potential target for preventing metastasis in broad cancer types at an early stage, which is much better than to have to treat it later on.”

While intratumour bacteria was found to have a clear role in promoting cancer cell metastatic colonisation, the authors did not exclude the possibility that the gut microbiome and immune system may act together with intratumour bacteria to determine cancer progression. Future in-depth analyses of how bacteria invade tumour cells, how intracellular bacteria are integrated into the host cell system, and how bacteria-containing tumor cells interact with the immune system will help inform how to properly deploy antibiotics in cancer treatment.

Source: ScienceDaily

Experiment Turns Back the Age of Human Skin Cells by 30 Years

This normal human skin cell was treated with a growth factor that triggered the formation of specialised protein structures that enable the cell to move.
Credit: Torsten Wittmann, University of California, San Francisco

In a finding which could revolutionise regenerative medicine, researchers have found a way to reverse the age of human skin cells by 30 years, reversing genetic ageing measures for cells without losing their specialised function. The function of older cells was partly restored, as well as rejuvenating the molecular measures of biological age. The research was published in the journal eLife.

One of the ways regenerative medicine aims to replace damaged or old cells is by creating ‘induced’ stem cells, which differentiate into specialised cells. Currently the process is not reversible.

The new method, based on stem cell production, overcomes the problem of entirely erasing cell identity by halting reprogramming part of the way through the process. This let researchers find the precise balance between reprogramming cells, making them biologically younger, while still being able to regain their specialised cell function.

Currently, cell reprogramming takes around 50 days using four key molecules called the Yamanaka factors. The new method, called ‘maturation phase transient reprogramming’, exposes cells to Yamanaka factors for just 13 days. At this point, age-related changes are removed and the cells have temporarily lost their identity. The partly reprogrammed cells were given time to grow under normal conditions, to observe whether their specific skin cell function returned. Genome analysis showed that cells had regained markers characteristic of skin cells (fibroblasts), and this was confirmed by observing collagen production in the reprogrammed cells.

To show that the cells had been rejuvenated, the researchers looked for changes in ageing indicators. Dr Diljeet Gill, who conducted the work as a PhD student explained: “Our understanding of ageing on a molecular level has progressed over the last decade, giving rise to techniques that allow researchers to measure age-related biological changes in human cells. We were able to apply this to our experiment to determine the extent of reprogramming our new method achieved.”

Cellular ages examined included the epigenetic clock, where chemical tags present throughout the genome indicate age. Another is the transcriptome, all the gene readouts produced by the cell. According to these two measures, the reprogrammed cells matched the profile of cells that were 30 years younger compared to reference data sets.

However, ‘rejuvenated’ cells need to function as if they were younger as well as looking younger. The rejuvenated fibroblasts were able to produce more collagen proteins compared to control cells that did not undergo the reprogramming process. Fibroblasts also move into areas that need repairing. Researchers tested the partially rejuvenated cells in vitro, and the treated fibroblasts moved into the gap faster than older cells – a sign that these could be used to improve wound healing,

The method also had an effect on other genes linked to age-related diseases and symptoms, the researchers saw, indicating possible future therapies. The APBA2 gene, associated with Alzheimer’s disease, and the MAF gene with a role in the development of cataracts, both showed changes towards youthful levels of transcription.

The researchers plan to explore the mechanism behind the successful transient programming, which is not yet completely understood. It is speculated that key areas of the genome involved in shaping cell identity might escape the reprogramming process.

Dr Diljeet concluded: “Our results represent a big step forward in our understanding of cell reprogramming. We have proved that cells can be rejuvenated without losing their function and that rejuvenation looks to restore some function to old cells. The fact that we also saw a reverse of ageing indicators in genes associated with diseases is particularly promising for the future of this work.”

Professor Wolf Reik, a group leader in the Epigenetics research programme who has recently moved to lead the Altos Labs Cambridge Institute, said: “This work has very exciting implications. Eventually, we may be able to identify genes that rejuvenate without reprogramming, and specifically target those to reduce the effects of ageing. This approach holds promise for valuable discoveries that could open up an amazing therapeutic horizon.”

Source: Babraham Institute

Avoid Goat’s Milk Skin Products in Inflammatory Skin Conditions

Photo by Robin Worrall on Unsplash

Individuals with inflammatory skin conditions should avoid using skincare products that contain food products such as goat’s milk, according to a series of case studies published in Clinical & Experimental Allergy. Such skincare products have been marketed to those with ‘sensitive skin’.

In children, milk allergy is one of the most common food allergies, but usually resolves in the first years of life. Adult-onset milk allergy is rare. In patients with inflammatory conditions of the skin such as atopic dermatitis, associations between the use of food allergen-containing skin products and systemic sensitisation to that foodstuff has been demonstrated for several foods. This is of concern, as food-containing skin products are commonly promoted as a safer and more ‘natural’ way of managing a variety of skin conditions. These are widely available for unprescribed purchase in pharmacies and supermarkets.

The present study reports on seven patients with inflammatory skin conditions who experienced anaphylaxis after ingesting goat’s or sheep’s milk or cheese products.  All of the patients had a history of using goat’s milk skin products to treat their skin conditions prior to the onset of their allergic reaction. Six of them had atopic dermatitis.

“Marketing of skin products derived from goat’s milk is extensive and targeted to patients with ‘sensitive skin’ who commonly have underlying inflammatory skin conditions,” the authors wrote. “Our findings provide novel evidence of the origins of adult-onset milk allergy and adds to the growing body of evidence that use of foodstuffs as therapy for inflammatory skin conditions can lead to the development of new food allergies.” 

Source: Wiley

Many Clinical Trials Ignore Previous Research

Photo by Louise Reed on Unsplash

Researchers evaluating a random selection of clinical trials done in North America found that they neglected to take into account previous or ongoing trials, which may result in researchers conducting redundant or less impactful studies. The findings were published in the journal Med.

Clinical trials are a crucial tool for assessing the safety and efficacy of medical interventions, but sponsors often provide incomplete information for assessing their ethical justification. Incomplete portrayals of supporting evidence hamper the ability of individuals or authorities to evaluate the trials’ risks, benefits, and scientific merit. 

To assess the prevalence of such omissions, researchers accessed the ClinicalTrials.gov registry and evaluated 101 randomly chosen clinical trials. Among those where there was at least one previous trial testing the same drug in the same disease, 30% of industry-sponsored trials and 20% of non-industry-funded trials failed to cite related studies. “Clinical trial protocols undercite easily accessible, relevant trials and do not document systematic searches for relevant clinical trials,” the authors wrote.

“Numerous studies suggest that some clinical trials are pursued despite their clinical hypotheses having been resolved prior to study launch,” write the authors. “Failure to provide a complete and impartial account of prior and ongoing research in study protocols may enable clinical research that fails to inform clinical practice.”

Source: EurekAlert