Tag: 22/11/24

Categories : Gastrointestinal Neurodegenerative DiseasesTags :

Parkinson’s Drug Found to Promote Pathogenic Gut Bacteria

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Fig. 1: Chemical imaging of active gut microbes. After brief incubation with heavy water, culture medium and a drug, various chemical bonds (here C-D and C-H) in the stool sample are shown in yellow and green, their ratio in yellow-purple (left). Selected microbes are detected in the same image section with fluorescence-labelled oligonucleotide probes in cyan. The activity of the detected microbes can be determined based on the amount of C-D bonds. C: Xiaowei Ge (Boston University)

An international team of scientists have revealed that the widely prescribed Parkinson’s disease drug entacapone significantly disrupts the human gut microbiome by inducing iron deficiency. This international study, provides new insights into the often-overlooked impact of human-targeted drugs on the microbial communities that play a critical role in human health. The findings, published in Nature Microbiology, suggest however that iron supplementation can help counteract these impacts.

While it is well established that antibiotics can significantly disrupt the human gut microbiome, emerging research shows that a wide range of human-targeted drugs – particularly those used to treat neurological conditions – can also profoundly affect the microbial communities living in our bodies. Despite their intended therapeutic effects on different organs, these drugs can inadvertently disrupt the balance of gut microbes, leading to potential health consequences. Until now, most studies investigating these interactions relied either on patient cohort analyses affected by many confounding factors or on experiments using isolated gut bacteria, which do not fully capture the complexity of the human microbiome.

Investigating drug–bug interactions

The team, which included some from the University of Vienna, used a novel experimental approach. The researchers studied the effects of two drugs – entacapone and loxapine, a medication for schizophrenia – on faecal samples from healthy human donors. They incubated the samples with therapeutic concentrations of these drugs, then analysed the impact on the microbial communities using advanced molecular and imaging techniques, including heavy water labelling combined with Stimulated Raman Spectroscopy (SRS). The team discovered that loxapine and even more so entacapone severely inhibited many microbiome members, while E. coli dramatically expanded in the presence of entacapone.

“The results were even more striking when we examined microbial activity, rather than just their abundance,” explained Fatima Pereira, lead author of the study and former Postdoctoral researcher at the University of Vienna. “The heavy water-SRS method allowed us to observe the subtle yet significant changes in the gut microbiome, which are often missed in traditional abundance-based measurements.”

Entacapone induces iron starvation, favours pathogenic microbes

The researchers hypothesised that entacapone might interfere with iron availability in the gut, a crucial resource for many microbes. Their experiments confirmed that adding iron to faecal samples containing entacapone counteracted the drug’s microbiome-altering effects. Further investigation revealed that E. coli, which thrived under these conditions, carried a highly efficient iron-uptake system (enterobactin siderophore). This system allowed the bacteria to overcome iron starvation and proliferate, even in the presence of the drug.

“By showing that entacapone induces iron deficiency, we have uncovered a new mechanism of drug-induced gut dysbiosis, in which the drug selects for E. coli and other potentially pathogenic microbes well adapted to iron limiting conditions,” said Michael Wagner, scientific director of the Excellence Cluster and vice-head of the Centre for Microbiology and Environmental Systems Science (CeMESS) at the University of Vienna.

Wider implications for drug–microbiome interactions

This discovery has broader implications for understanding how other human-targeted drugs might affect the gut microbiome. Several drugs, including entacapone, contain metal-binding catechol groups, suggesting that this mechanism could be a more common pathway for drug-induced microbiome alterations.

The findings also present an opportunity to mitigate the side effects of drugs like entacapone. By ensuring sufficient iron availability to the large intestine, it may be possible to reduce dysbiosis and the gastrointestinal issues that often accompany Parkinson’s disease treatment.

“The next step is to explore how we can modify drug treatments to better support the gut microbiome,” said Wagner. “We are looking at strategies to selectively deliver iron to the large intestine, where it can benefit the microbiome without interfering with drug absorption in the small intestine.”

Source: University of Vienna

Categories : Medical Industry Obstetrics & GynaecologyTags :

Bayer Issues Recall on YAZ Plus Contraceptive Pills

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Photos supplied by Bayer showing the affected blister (left) and the normal blister (right).

On November 21, Bayer (Pty) Ltd issued a medicine recall for a specific batch (WEW96J) of YAZ PLUS tablets. In a press release, they explain the reason for the recall: it has been discovered that the active and inactive tablets in this batch are swapped. This mix-up has resulted in some packs containing only four hormone tablets instead of the required 24, and 24 hormone-free tablets instead of four, compromising the product’s contraceptive efficacy.

The company advises that healthcare professionals, wholesalers, hospitals, retail pharmacy outlets, doctors, nurses, pharmacists, authorised prescribers, dispensers, and individual customers or patients in possession of the affected batch can return product to their healthcare facility from which it was dispensed, for credit.

Bayer urges that if you are in possession of YAZ PLUS tablets from the affected batch, to do the following:

  1. Stop Use Immediately: If you have been taking the tablets from a batch that is affected with the mix-
    up, stop taking them immediately and contact your healthcare professional. While only a limited number of packs from the respective batch is affected, as a precautionary measure, no tablets from these packs shall be used until you have consulted your Healthcare Practitioner, as they may potentially not provide the contraceptive protection you expect.
  2. Return the Product: Please return any affected packs to the pharmacy or retailer where you
    purchased them for a replacement or refund.
  3. Check Your Packs: If you have multiple packs of YAZ PLUS, please check each one of them, to
    ensure they are not from the affected batch.
  4. Consult Healthcare Provider: If you have consumed tablets from the affected batch, or if you have
    concerns about your contraceptive coverage, please consult your healthcare provider as soon as
    possible for advice.

In the press release, Bayer says that it “takes the safety and efficacy of its products seriously and is committed to ensuring that all YAZ PLUS tablets in the market meet the highest quality standards.” It further advises that the root cause for the mix-up of tablets in the packaging has been identified and corrective measures taken. Only this one batch – and no others – was affected.

“The company is working diligently with SAHPRA and healthcare providers to facilitate the recall process and minimise any inconvenience to our customers. We are dedicated to addressing this issue promptly and ensuring the continued health and safety of all our customers.”

Further Information and Support:
For more information about this recall, or if you have any questions or concerns, please contact Bayer +27
(0) 11 921 5000. Our team is available to provide the support and information you need.
Report a side effect: Patient Safety Reporting – Introduction
Report a product quality complaint for Pharmaceutical Products: afptc@bayer.com

Categories : Obstetrics & GynaecologyTags :

Short-term Menopausal Hormone Therapy has no Long-term Cognitive Impact

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Photo by Teona Swift on Unsplash

Women in early postmenopause taking short-term MHT had no cognitive effects a decade later

Short-term menopausal hormone therapy (MHT) did not have long-term cognitive effects when given to women in early postmenopause, according to a study published November 21st in the open-access journal PLOS Medicine by Carey Gleason from the University of Wisconsin-Madison, USA, and colleagues.

While MHT can offer relief from the challenging symptoms of menopause, many women and doctors are hesitant to start MHT due to safety concerns. Previous research has linked one form of hormone therapy to mild cognitive impairment and dementia in women older than 65 years of age, prompting research on the importance of age and timing of therapy on cognitive impairment. Other studies have suggested that transdermal oestrogen may have long-term cognitive benefits.

In the Kronos Early Estrogen Prevention Study (KEEPS), women in early postmenopause with good cardiovascular health were randomised to receive one of two types of MHT (oral or transdermal oestrogen) or placebo. At the end of four years, no cognitive benefit or harm was seen in those who received MHT compared to the placebo group. However, long-term cognitive effects of MHT are still understudied.

In this new follow-up study – the KEEPS Continuation Study – researchers revisited participants nearly ten years later to repeat a series of cognitive tests. Among 275 women, although MTH failed to protect against cognitive decline, short-term MHT also had no long-term negative cognitive impact.

These findings may offer reassurance to women considering MHT while adding to the growing body of research supporting the importance of timing for MHT. More research is needed to investigate whether these results are generalisable to women with higher cardiovascular risk.

The authors add, “For women in menopause and the health care providers caring for them, getting direct, clear and evidence-based information about menopausal hormone therapy is challenging. And they need data to guide their decisions.”

Provided by PLOS

Categories : Exercise NeurologyTags :

Workouts – or Disturbed Sleep – Impact Brain Activity Weeks Later

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Photo by Ketut Subiyanto on Pexels

In a rare, longitudinal study, researchers from Aalto University and the University of Oulu tracked one person’s brain and behavioural activity for five months using brain scans and data from wearable devices and smartphones. The results appear in PLOS Biology.

“We wanted to go beyond isolated events,” says research leader (and study participant) Ana Triana. “Our behaviour and mental states are constantly shaped by our environment and experiences. Yet, we know little about the response of brain functional connectivity to environmental, physiological, and behavioural changes on different timescales, from days to months.”

The study found that the brain does not respond to daily life in immediate, isolated bursts. Instead, brain activity evolves in response to sleep patterns, physical activity, mood, and respiration rate over many days. This suggests that even a workout or a restless night from last week could still affect the brain – and therefore attention, cognition and memory – well into next week.

The research also revealed a strong link between heart rate variability – a measure of the heart’s adaptability – and brain connectivity, particularly during rest. This suggests that impacts on the body’s relaxation response, like stress management techniques, could shape brain wiring even when not actively concentrating on a task. Physical activity was also found to positively influence the way brain regions interact, potentially impacting memory and cognitive flexibility. Even subtle shifts in mood and heart rate left lasting imprints for up to 15 days.

Study goes beyond a snapshot

The research is unusual in that few brain studies involve detailed monitoring over days and weeks. “The use of wearable technology was crucial,” says Triana. “Brain scans are useful tools, but a snapshot of someone lying still for half an hour can only show so much. Our brains do not work in isolation.”

Triana was herself the subject of the research, monitored as she went about her daily life. Her unique role as both lead author and study participant added complexity, but also brought firsthand insights into how best to maintain research integrity over several months of personalised data collection.  Data from the devices and twice-weekly brain scans were complemented by qualitative data from mood surveys. 

The researchers identified two distinct response patterns: a short-term wave lasting under seven days and a long-term wave up to 15 days. The former reflects rapid adaptations, like how focus is impacted by poor sleep, but it recovers quickly. The long wave suggests more gradual, lasting effects, particularly in areas tied to attention and memory. 

Single-subject studies offer opportunities for improving mental health care 

The researchers hope their innovative approach will inspire future studies that combine brain data with everyday life to help personalise mental health treatment. 

“We must bring data from daily life into the lab to see the full picture of how our habits shape the brain, but surveys can be tiring and inaccurate,” says study co-author, neuroscientist and physician Dr Nick Hayward. “Combining concurrent physiology with repeated brain scans in one person is crucial. Our approach gives context to neuroscience and delivers very fine detail to our understanding of the brain.”

The study is also a proof-of-concept for patient research. Tracking brain changes in real time could help detect neurological disorders early, especially mental health conditions where subtle signs might be missed.

“Linking brain activity with physiological and environmental data could revolutionise personalised healthcare, opening doors for earlier interventions and better outcomes,” says Triana.

Source: Aalto University

Categories : Cardiovascular Disease Regenerative MedicineTags :

Human Hearts may Possess a Latent Ability to Regenerate Cardiomyocytes

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

After severe heart failure, the ability of the heart to heal by forming new cells is very low. But now Karolinska Institutet researchers found that, after use of a supportive heart pump, the capacity of a damaged heart to repair itself with new cardiomyocytes becomes significantly higher – even greater than that of a healthy heart. This study is published in the journal Circulation.

The ability of the human heart to renew itself by regenerating its muscle cells, myocytes, is very limited. But what happens to this capability when the heart is damaged by severe heart failure has been unknown.

Researchers at Karolinska Institutet have now discovered that after an injury, the rate of cell renewal is even lower than in a healthy heart. Standard-of-care for patients with advanced heart failure is a surgically implanted pump that helps propel blood, a so-called left ventricular assist device (LVAD).

Kick-starting repair

Surprisingly, the researchers found that patients with such a heart pump, who have shown significant improvement in their heart function, can regenerate heart muscle cells at a rate more than six times higher than in healthy hearts.

“The results suggest that there might be a hidden key to kick-start the heart’s own repair mechanism”, says Olaf Bergmann, senior researcher at the Department of Cell and Molecular Biology at Karolinska Institutet and last author of the paper.

The mechanism behind the effect is still unknown and there is not yet any hypothesis to explain it.

“It is difficult to say. In the existing data we cannot find an explanation for the effect, but we will now continue to study this process at a cellular and molecular level,” says Olaf Bergmann.

The findings open the possibility of developing new therapies for patients with serious heart conditions that stimulate the heart’s ability to repair itself after damage. This way, patients wouldn’t have to rely only on heart transplants or other kinds of long-term mechanical support.

“This offers some hope that the recovery after a heart incident can somehow be boosted,” says Olaf Bergmann.

Atomic bombs enable cell age estimation

It is generally difficult to determine the age of cells in the human body and to decide which cells are new and which are old. However, by using a method earlier devised by Jonas Frisén, professor of stem cell research at Karolinska Institutet, the group has been able to count the rate of renewal of myocytes in the heart. The method is based upon the fact that the percentage of radioactive carbon in the atmosphere, and subsequently in our cells, has steadily decreased since the nuclear test ban in 1963. For every following year, there is a little less radioactivity in newly formed cells, which means that they can be ‘dated’. 

Source: Karolinska Institute