Day: August 4, 2022

Sun Exposure Triggers Appetite in Men but not Women

Photo by Julian Jagtenberg on Pexels

A new study from Tel Aviv University reveals that solar exposure increases appetite in males – but not in females. It is the first gender-dependent medical study ever conducted on UV exposure, and reveals a molecular connection between UV exposure and appetite.

Skin as a regulator of appetite

The groundbreaking study was led by Prof. Carmit Levy and PhD student Shivang Parikh and published in Nature Metabolism.

The study was based on epidemiological data collected in a year-long survey about the eating habits of approximately 3000 Israelis of both sexes, including self-reports from students who had spent time in the sun, combined with the results of a genetic study in a lab model. The findings identify the skin as a primary regulator of metabolism in both lab models and humans, influencing appetite.

In females, oestrogen blocks appetite after sun exposure

The study unravels the differences between males and females in the activation of the metabolic mechanism. The researchers explain that in males of both animal species and humans, sun exposure activates a protein called p53, to repair any DNA damage in the skin that might have been caused by the exposure. The activation of p53 signals the body to produce a hormone called ghrelin, which stimulates the appetite.

In females, oestrogen blocks the interaction between p53 and ghrelin, and consequently does not catalyse the urge to eat following exposure to the sun.

Males and females, have differences in metabolism which impacts both their health and their behaviour. However, so far it has not been established whether the two sexes respond differently to environmental triggers such as exposures to the sun’s UV radiation.

“We examined the differences between men and women after sun exposure and found that men eat more than women because their appetite has increased. Our study was the first gender-dependent medical study ever conducted on UV exposure, and for the first time, the molecular connection between UV exposure and appetite was deciphered. Gender-dependent medical studies are particularly complex, since twice the number of participants is required to find statistically significant differences,” explained Prof Levy.

“As humans, we have cast off our fur and consequently, our skin, the largest organ in our body, is exposed to signals from the environment. The protein p53, found in the skin, repairs damage to the DNA caused by sun exposure, but it does more than that. It signals to our bodies that winter is over, and we are out in the sun, possibly in preparation for the mating season. Our results provide an encouraging basis for more research, on both human metabolism and potential UV-based therapies for metabolic diseases and appetite disorders,” Prof Levy concluded.

Source: Tel Aviv University

Assessing the Effectiveness of Chinese Traditional Medicine for Rheumatoid Arthritis

Hand osteoarthritis
Source: Pixabay CC0

Chinese traditional medicine based on combinations of typically 5 to ten plants, usually boiled and administered as a decoction or tea, has long been used to treat rheumatoid arthritis (RA), but few clinical trials have tested its potential. A review in the Journal of Internal Medicine outlines a strategy to analyse the ability of different mixtures of plants used in Chinese medicine to combat RA.

One fundamental of traditional medicine is to prevent disease. RA is an autoimmune, inflammatory and chronic disease that primarily affects the joints of 0.5%–1% of the population. In two out of three of the cases, the patients are characterised by the presence of autoantibodies such as the rheumatoid factor and the more disease-specific autoantibody against citrullinated proteins, so-called ‘ACPA’ (anticitrullinated protein/peptide antibodies). ACPA positivity is also strongly associated with specific variations in the HLA-DRB1 gene, the shared epitope alleles. Together with smoking, these factors account for the major risks of developing RA. 

The researchers’ strategy involves isolating the active components of individual plants and testing them alone or in combinations against key pathways of disease pathology, followed by experiments conducted in animal models of RA.

“A substantial number of our current drugs are natural products or derivatives thereof, and without doubt nature will continue to be a source of future discoveries,” the authors wrote. “Therefore continuous research based on the traditional use of plants is highly motivated. In our opinion, the strategy of starting from knowledge in traditional medicine, followed by the combination of in vivo evidence of efficacy and bioassay-guided isolation to understand the chemistry and pathways involved, is one effective way forward.”

Source: Wiley

Focus on Urinary Problems Clouds Early Prostate Cancer Detection

Credit: Darryl Leja / National-Human-Genome Research Institute / National Institutes of Health

Diagnoses of early, curable stages of prostate cancer are being missed because national guidelines and media health campaigns in the UK focus on urinary symptoms despite a lack of scientific evidence, according to University of Cambridge researchers.

Prostate cancer is the most common type of cancer in men. And while 78% of men diagnosed with this cancer survive for over ten years, this proportion has barely changed over the past decade in the UK, largely because the disease is detected at a relatively late stage. In England, for example, nearly half of all prostate cancers are picked up at stage three of four (stage four being the latest stage).

Despite no evidence of a link between urinary symptoms and prostate cancer, national guidelines, health advice and public health campaigns continue to promote this link. In a review published in BMC Medicine, Cambridge researchers argue that not only is this unhelpful, but it may even deter men from coming forward for early testing and detection of a potentially treatable cancer.

“When most people think of the symptoms of prostate cancer, they think of problems with peeing or needing to pee more frequently, particularly during the night,” said Vincent Gnanapragasam, Professor of Urology at the University of Cambridge. “This misperception has lasted for decades, despite very little evidence, and it’s potentially preventing us picking up cases at an early stage.”

Prostate enlargement can cause the urinary problems often included in public health messaging, but evidence suggests that this is rarely due to malignant prostate tumours. Rather, research suggests that the prostate is smaller in cases of prostate cancer.  A recent study – the UK PROTECT trial – even went as far as to say that a lack of urinary symptoms may in fact be an indicator of a higher likelihood of cancer.

Screening programmes are one way that cancers are often detected at an early stage, but in the case of prostate cancer, some argue that such programmes risk overwhelming health services and leading to men being treated for relatively benign disease.

Testing for prostate cancer involves a blood test that looks for a protein known as a prostate-specific antigen (PSA) that is made only by the prostate gland; however, it is not always accurate. PSA density is significantly more accurate than PSA alone in predicting a positive biopsy and is used in everyday clinical practice.

The researchers point to evidence that there is a misconception that prostate cancer is always symptomatic: a previous study found that 86% of the public associated prostate cancer with symptoms, but only 1% were aware that it could be asymptomatic.

“We urgently need to recognise that the information currently given to the public risks giving men a false sense of security if they don’t have any urinary symptoms,” said Prof Gnanapragasam.

“We need to emphasise that prostate cancer can be a silent or asymptomatic disease, particularly in its curable stages. Waiting out for urinary symptoms may mean missing opportunities to catch the disease when it’s treatable.

“Men shouldn’t be afraid to speak to their GP about getting tested, and about the value of a PSA test, especially if they have a history of prostate cancer in their family or have other risk factors such as being of Black or mixed Black ethnicity.”

The researchers say they are not advocating for an immediate screening programme, and acknowledge that changes in messaging could mean more men approaching their GPs for a PSA test, potentially resulting in unnecessary investigations and treatment. However, they argue that there are ways to reduce the risk of this happening. These include the use of algorithms to assess an individual’s risk and whether they need to be referred to a specialist, and for those who are referred, MRI scans could help rule out ‘indolent’ (mild) disease or negative findings, reducing the risks of an unnecessary biopsy.

“We’re calling on organisations such as the NHS, as well as patient charities and the media, to review the current public messaging,” said Prof Gnanapragasam.

“If men were aware that just because they have no symptoms doesn’t necessarily mean they are cancer free, then more might take up offers for tests. This could mean more tumours identified at an earlier stage and reduce the numbers of men experiencing late presentation with incurable disease.”

Source: University of Cambridge

New Tuberculosis Vaccine Passes Safety Hurdle in SA Trial

Tuberculosis bacteria
Tuberculosis bacteria. Credit: CDC

The only vaccine currently available against tuberculosis, Bacillus Calmette Guérin (BCG), is not equally effective against all types of tuberculosis. A clinical trial in South Africa has now shown that the new vaccine candidate VPM1002, decades in development, is equally safe for newborns with and without HIV exposure and has fewer side effects compared to BCG.

First used 100 years ago, the BCG vaccine against the disease contains attenuated pathogens of cattle tuberculosis. “We know that BCG can prevent so-called tuberculous meningitis and miliary tuberculosis in infants with a 75 to 86 percent effectiveness rate. But this is not the case for the most common form of the disease, pulmonary tuberculosis, in all age groups. Here, BCG is only insufficiently effective,” explained Max Planck researcher Stefan H.E. Kaufmann, who developed the vaccine with his team.

Since the 1990s, the infection biologist and his team have been working on an improved next-generation vaccine, called VPM1002. To achieve this, the researchers genetically modified the attenuated BCG vaccine strain so that immune cells can better recognise the pathogens. “We developed VPM1002 in no small part to combine increased safety with improved efficacy for immunocompromised children,” Kaufmann said.

Vaccine candidate VPM1002 is safe

The group of immunocompromised children includes, for example, HIV-exposed infants born to HIV-positive mothers. In a clinical trial in South Africa, researchers compared VPM1002 with BCG in HIV-exposed and non-HIV-exposed newborns. The study examined both the safety and the immunogenicity associated with the formation of immune cells and immunostimulatory proteins. The study, published in Lancet Infectious Diseases, concluded that VPM1002 is safe in both HIV-exposed and non-HIV-exposed newborns, has fewer side effects than BCG, and elicits a similar immune response.

In the randomised phase II double-blind study in South Africa, 416 eligible newborns were randomly selected and vaccinated before day 12 of life. 312 of them received VPM1002, and 104 received the BCG vaccine. As the study showed, VPM1002 triggered fewer vaccine-related adverse reactions than BCG. This was true for reactions occurring at the injection site, such as scarring and abscess formation, as well as enlargement of lymph nodes. This finding is important because local and regional reactions after vaccination are among the limitations of the BCG vaccine, Kaufmann points out.

Newborns with or without HIV exposure showed similar immunogenicity with both vaccines, though starting at six weeks of age, the BCG-triggered immune response was greater than in even younger infants.

Phase III study investigates protection

“Studies such as those described here examine a vaccine’s immunogenicity, but not its protection. For the latter, we have already developed a larger phase III clinical trial and have successfully enrolled mothers with their newborns to participate. Now the clock is ticking,” Kaufmann said. He expects initial results showing whether VPM1002 can provide comparable or better protection than existing BCG vaccines in about three years. In addition, VPM1002 vaccine is currently in two other phase III clinical trials in India for protection against tuberculosis, which expected to be completed in 2023 and 2024.

Source: Max-Planck-Gesellschaft

Gout Flare-ups Linked to Increased MI and Stroke Risk

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The risk of myocardial infarction (MI) and strokes temporarily increases in the four months after a gout flare, suggests a study published in the journal JAMA.

The findings showed that gout patients who suffered from an MI or stroke were twice as likely to have had a gout flare in the 60 days prior to the event, and one and a half times more likely to have a gout flare in the 61-120 days prior.

Gout is a common form of arthritis that is caused by high levels of uric acid, a chemical produced by breakdown of body tissues and present in certain foods and drinks.

At high levels, uric acid is deposited in and around joints as needle shaped urate crystals. Once released from their deposits, these crystals cause severe inflammation that manifest as joint pain, swelling, redness, and tenderness that often lasts for 1–2 weeks. These episodes, called gout flares, often recur. Inflammation is also a risk factor for heart attack and stroke.

While gout patients tend to have more cardiovascular risk factors, there have been no previous studies about whether gout flares are linked with an increased risk of MI and stroke.

To address this, the team used data from 62 574 patients with gout treated in the NHS. Of these, 10 475 experienced heart attack or stroke after the diagnosis of gout, while matched controls did not experience such events. They evaluated the association between heart attacks or strokes and recent gout flares and adjusted these results for possible confounding factors. They found that gout patients who suffered an MI or stroke were twice as likely to have had a gout flare in the 60 days prior to the event, and one and a half times more likely to have a gout flare in the preceding 61–120 days.

They found a similar high rate of MI or stroke in the 0–60 and 61–120 days after gout flares compared with other time periods, when they used information from only patients who consulted for a gout flare and also experienced either MI or stroke. This further strengthened the finding that gout flares are associated with a transient increase in cardiovascular events following flares. The increased odds and rates persisted when people with pre-existing heart disease or stroke before their gout diagnosis were excluded, and when shorter exposure periods such as 0-15 and 16-30 days prior to MI or stroke, were considered.

Gout patients who died from a MI or stroke had over four times the odds of experiencing a gout flare in the preceding 0-60 days and over twice the odds of gout flare in the preceding 61-120 days.

The study’s lead author, Professor Abhishek at the University of Nottingham, said: “This is the first study of its kind to examine whether there is an association between recent gout flares and heart attacks and strokes.

“The results show that among patients with gout, patients who experienced a heart attack or stroke had significantly increased odds of a gout flare during the preceding 120-days compared with patients who did not experience such events. These findings suggest that gout flares are associated with a transient increase in cardiovascular events following flares.

“People with recurrent gout flares should be considered for long-term treatment with urate lowering treatments such as allopurinol. This is a reliable way of removing urate crystal deposits and providing freedom from gout flares. Patients should also be considered for concurrent treatment with anti-inflammatory medicines such as colchicine for the first few months because urate lowering treatments may trigger gout flares in the short term.

“People with gout should be encouraged to adopt a healthy lifestyle with appropriate treatment of conditions such as high blood pressure, high cholesterol, obesity and diabetes to minimise their background risk of heart attack and stroke.”

Source: University of Nottingham