Day: September 4, 2025

Categories : Metabolic DisordersTags : Leave a comment

Metformin Found to Change Blood Metal Levels in Humans

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Although metformin is the most widely prescribed diabetes drug in the world, its mechanism of action is still not clear. Kobe University endocrinologist OGAWA Wataru has now made significant progress, finding that it changes blood metal levels in humans. Photo by Towfiqu Barbhuiya on Unsplash

The widely used diabetes drug metformin may achieve its effects by changing blood metal levels in humans. The Kobe University study is an important step in understanding the drug’s many actions and designing better ones in the future.

Metformin is the most widely prescribed diabetes drug in the world. Apart from lowering blood sugar levels, it is also known to have a broad range of beneficial side effects such as against tumours, inflammations and atherosclerosis. However, although it has been used for more than 60 years now, its mechanism of action is still not clear, hampering the development of even better drugs against these conditions.

Kobe University endocrinologist OGAWA Wataru says: “It is known that diabetes patients experience changes in the blood levels of metals such as copper, iron and zinc. In addition, chemical studies found that metformin has the ability to bind certain metals, such as copper, and recent studies showed that it is this binding ability that might be responsible for some of the drug’s beneficial effects. So, we wanted to know whether metformin actually affects blood metal levels in humans, which had not been clarified.” To do so, Ogawa and his team enlisted about 200 diabetes patients at Kobe University Hospital, half of which took metformin and half of which did not, in a study to analyse their blood serum levels for those metals and various metal deficiency indicators.

In the journal BMJ Open Diabetes Research & Care, the Kobe University team now published the first clinical evidence of altered blood metal levels in patients taking metformin. They showed that drug-taking patients have significantly lower copper and iron levels and heightened zinc levels. Ogawa says: “It is significant that we could show this in humans. Furthermore, since decreases in copper and iron concentrations and an increase in zinc concentration are all considered to be associated with improved glucose tolerance and prevention of complications, these changes may indeed be related to metformin’s action.”

Recently, Japan has approved the use of imeglimin, a new diabetes drug that is a derivative of metformin but that should not be able to bind metals the same way as its parent. “Imeglimin is thought to have a different method of action, and we are already conducting studies to compare the effects the two drugs have,” says Ogawa.

It is not just about understanding the current drugs, however. Ogawa explains the bigger picture, saying: “We need both clinical trials and animal experiments to pinpoint the causal relationship between the drug’s action and its effects. If such studies progress further, they may lead to the development of new drugs for diabetes and its complications by properly adjusting the metal concentrations in the body.”

Source: Kobe University

Categories : Implants and Prostheses Metabolic DisordersTags : Leave a comment

Implant Treats Type 1 Diabetes by Oxygenating Insulin-producing Cells

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A 3D map of the islet density routes throughout the healthy human pancreas. Source: Wikimedia CC0

Cornell researchers have developed an implant system that can treat Type 1 diabetes by supplying extra oxygen to densely packed insulin-secreting cells, without the need for immunosuppression. The system could also potentially provide long-term treatment for a range of chronic diseases.

The findings appear in Nature Communications. The co-first authors were former postdoctoral researcher Tung Pham and doctoral candidate Lora (Phuong) Tran.

The technology builds off previous implantable encapsulation devices developed in the lab of Minglin Ma, professor of biological and environmental engineering in the College of Agriculture and Life Sciences (CALS) and the paper’s senior author.

Ma has explored a variety of ways to address Type 1 diabetes, which is typically managed through daily insulin injections or insulin pumps, but even with that treatment, patients still suffer the devastating effects of the disease.

Ma’s previous implantable devices have proved effective in controlling blood sugar in diabetic mice, but they can only last so long.

“One of the major challenges is the implant itself often dies due to the lack of oxygen after implantation,” Tran said. “In our lab, they had success in mice that lived over one year, and they controlled the diabetes very effectively with some small capsules without oxygen generation. However, when we scale up, we need more cells, we need more density, especially. We need a higher dose. If we implant without generating oxygen, the cells often die within two weeks.”

Ma’s team developed the new system in collaboration with electrochemical researchers from Giner Inc, including co-author Linda Tempelman, PhD ’93.

The key components of the system are a cylindrical capsule with a ring-shaped cross-section that contains transplanted insulin-secreting cells, and an electrochemical oxygen generator that is roughly the size of a dime and removeable. A nanofibrous membrane outside the capsule protects the cells from the host body’s immune system; a permeable membrane in the core of the capsule allows the central supply of oxygen to reach the ring of cells.

“We have to meet two requirements,” Tran said. “The first is immune protection. And second, you have to maintain mass transfer, like the glucose and other nutrients and molecules that can go in and out.”

Working with Dr James Flanders, associate professor emeritus in the College of Veterinary Medicine, the researchers successfully tested the system in rat models.

“It’s the proof of concept. We really proved that oxygenation is important, and oxygenation will support high cell-density capsules,” Tempelman said. “The capsules are immune protective and last for a long time without having some kind of fouling of the membrane. The body never likes when you put a foreign substance in. So that’s the engineering in the Ma Lab, to look for materials and coatings for the materials that are immune protective, but also don’t invoke excess response from the body because of the material.”

The new system would enable a much greater number of the 2 million people who suffer from Type 1 diabetes in the US to now have an islet transplant or cell therapy without requiring immune suppression, which is considered too dangerous for routine use. Also, the new system can provide much tighter sugar control, effectively curing the disease and enabling the person to eat, drink and exercise like everyone else. 

The next step will be to implant the system in a pig model, and also test it with human stem cells. The researchers are interested in eventually trying to use the system for implanting different cell types in humans for long-term treatment of chronic diseases, according to Tempelman, who is CEO of Persista Bio Inc., a new startup she founded with Ma and Flanders that is licensing these technologies.

“We see an age where people will be getting implants with allogeneic cells from other human beings, from stem cell lines, and using it long term to treat things that your body is missing,” Tempelman said. “Here we’re missing insulin. In pain control, maybe you need more endorphins or some other molecule. In enzyme replacement therapy, you need more enzymes. We’re interested in things like other autoimmune diseases where there’s inflammation that’s out of control.

“So maybe you could put a small molecule in that would treat inflammation, and then someone, like a Lupus patient, wouldn’t have to take an oral medication. They could just have a low-level implant that provides a low amount of it.”

Source: Cornell University

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Research Findings Offer New Insight into Heparin and Bone Builders

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Photo by Mufid Majnun on Unsplash

The blood thinner heparin is used during and after surgery and is essential to kidney dialysis. Most of today’s heparin comes from pigs, but the Federal Drug Administration is encouraging the use of alternative sources, including cows and synthetic forms of heparin, to diversify the supply chain.

Unfortunately, heparin from animals other than pigs just doesn’t work as well.

The reasons are connected to ongoing questions in modern cell biology. Now, an interdisciplinary Virginia Tech team has uncovered new molecular clues that may explain why some sources of heparin are more effective than others. The findings, published recently in the Proceedings of the National Academy of Sciences, may open doors for designing safer, more reliable heparin therapies.

“The structure of heparin and how that structure impacts function is an ongoing puzzle,” said Brenna Knight, first author of the study and recent graduate student studying in the Department of Chemistry. “Seemingly small differences in the content and arrangement of [chemical entities called] sulfates on the molecule cause substantial differences in the energetics that drive chemical activity.”

From mineralization to medicine

Heparin hails from a family called heparan sulfates, or heparans, present in all living creatures. These chains of sugars are diverse, serve many functions in organisms, and many, including heparin, are incredibly complex.

As a student of Patricia Dove in the Departments of Geosciences and Chemistry, Knight was originally looking at heparans for a completely different reason: to understand how the sulfates could impact biological mineralisation, which is the process by which organisms build crystal-strengthened tissues such as bones, teeth, shells, and corals.

Dove is one of today’s pre-eminent geochemists and was elected to the National Academy of Sciences in 2012. Unravelling the process of biomineralisation has been one of her major passions over the past three decades.  

“Animals grow crystals in specific places, usually to make structures that serve to support, defend, or feed themselves.” said Dove. “It’s a coordinated result of many chemical reactions within the organism and a crowning achievement of biology. We’ve been trying to better understand the reactions that produce these working biomaterials for a long time.”

That mineralization process unexpectedly linked back to medicine.

Heparan sulfates are just one of many different agents that interact with calcium to trigger a diverse portfolio of biochemical operations. One of those operations is integral to blood clotting.

Team science

To better understand how heparan sulfates help facilitate biomineralisation, Dove and Knight teamed with Kevin Edgar, professor in the Department of Sustainable Biomaterials, who was interested in heparans from the healthcare angle. To study interactions of calcium with heparin, they worked with Michael Schulz and graduate student Connor Gallagher in the chemistry department.  

When they applied their combined expertise to calcium-heparin interactions, they found that slight variations in heparin’s molecular composition changed how effective it was at binding calcium. These differences could affect its ability to form biominerals and blood thinners.  

“This paper provides insights for how to bioengineer synthetic pathways to effective heparin products for applications in therapeutics and drug delivery,” Edgar said.

Source: Virginia Tech

Categories : AntibioticsTags : Leave a comment

One Dose of Antibiotic Treats Early Syphilis as Well as Three Doses 

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NIH-funded clinical trial shows potential to simplify treatment for early syphilis.

Photo by Raghavendra V Konkathi on Unsplash

Researchers funded by the National Institutes of Health (NIH) have found that a single injection of the antibiotic benzathine penicillin G (BPG) successfully treated early syphilis just as well as the three-injection regimen used by many clinicians in the United States and elsewhere. These findings from a late-stage clinical trial suggest the second and third doses of conventional BPG therapy do not provide a health benefit. The results were published in The New England Journal of Medicine.

“Benzathine penicillin G is highly effective against syphilis, but the three-dose regimen can be burdensome and deter people from attending follow-up visits with their healthcare providers,” said Carolyn Deal, PhD, chief of the enteric and sexually transmitted infections branch of NIH’s National Institute of Allergy and Infectious Diseases (NIAID). “The new findings offer welcome evidence for potentially simplifying treatment with an equally effective one-dose regimen, particularly while syphilis rates remain alarmingly high.”

Syphilis is a common sexually transmitted infection (STI) caused by the bacterium Treponema pallidum. The United States reported 209 253 total syphilis cases and 3882 congenital syphilis cases in 2023, representing 61% and 108% increases over 2019 numbers, respectively. Without treatment, syphilis can result in neurological and organ damage as well as severe pregnancy complications and congenital abnormalities. Syphilis can also increase a person’s likelihood of acquiring or transmitting HIV.

BPG is one of the few antibiotics known to effectively treat syphilis, and stockouts are common worldwide. The antibiotic is currently being imported to the United States to resolve a nationwide shortage.

The study was conducted at ten U.S. sites and enrolled 249 participants with early syphilis, which encompasses the primary, secondary, and early latent stages of disease. Sixty-four percent of participants were living with HIV and 97% were men. The participants were randomly assigned to receive either a single intramuscular (IM) injection of BPG 2.4 million units (MU) or a series of three IM injections of BPG 2.4 MU at weekly intervals. All participants were monitored for safety. Biological markers of successful treatment in the blood – known as the serologic response to therapy – were examined at six months following treatment.

Seventy-six percent of participants in the single-dose group had a serologic response to treatment compared to 70% of participants in the three-dose group. The difference between groups was not statistically significant, even when participants were stratified by HIV status. One participant developed signs of neurosyphilis three days after starting BPG therapy and was excluded from the analysis. Three serious adverse events were reported but were not related to BPG.

“Syphilis has been studied and treated for more than a century, and BPG has been in use for more than 50 years, yet we are still acquiring knowledge to help us optimise treatment,” said Principal Investigator Edward W. Hook III, MD, emeritus professor of medicine and epidemiology at the University of Alabama at Birmingham. “We hope these promising results will be complemented by scientific advances in syphilis prevention and diagnosis.”

According to the study authors, the results from this trial provide substantial evidence that single-dose BPG 2.4 MU is as effective as three doses in treating early syphilis. More research is needed to understand the full potential of this abbreviated treatment strategy and to evaluate therapeutic approaches for all stages of syphilis, including late syphilis, latent syphilis of unknown duration, and clinical neurosyphilis.

The study was conducted through the NIAID-funded Sexually Transmitted Infections Clinical Trials Group.

For more information about this trial, please visit ClinicalTrials.gov using the study identifier  NCT03637660.

Source: National Institutes of Health

Categories : GastrointestinalTags : Leave a comment

Scrolling While on the Toilet Linked to Higher Risk of Haemorrhoids

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New study supports anecdotal claims about the risks of using a smartphone during toilet time

Photo by Jan Antonin Kolar on Unsplash

Survey participants who reported using a smartphone while on the toilet had a higher risk of haemorrhoids than non-users. Chethan Ramprasad of Beth Israel Deaconess Medical Center, U.S., and colleagues present these findings in a new study in the open-access journal PLOS One on September 3, 2025.

Every year in the US, haemorrhoids lead to nearly 4 million visits to the doctor or emergency room and more than $800 million in healthcare spending. Haemorrhoids involve swollen veins in the anal or rectal area and can cause pain and bleeding. Anecdotal evidence has linked smartphone use on the toilet with increased risk of haemorrhoids.

However, few studies have explored whether smartphone use on the toilet is actually associated with haemorrhoid risk. To help clarify, Ramprasad and colleagues conducted a study of 125 adults undergoing screening colonoscopy. The participants answered online survey questions about their lifestyle and toilet habits, and endoscopists evaluated them for haemorrhoids.

Among all participants, 66% reported using smartphones on the toilet, and they tended to be younger than non-users. After statistically accounting for other factors thought to possibly be linked with haemorrhoid risk – such as exercise habits, age, and fibre intake – the researchers found that participants who used a smartphone on the toilet had a 46% higher risk of haemorrhoids than non-users.

Time spent on the toilet was significantly higher for smartphone users than non-users; 37% of smartphone users spent more than 5 minutes at a time on the toilet compared to just 7.1% of non-users. Reading news and using social media were the most commonly reported smartphone activities on the toilet. Interestingly, straining while using the toilet was not associated with increased haemorrhoid risk, in contrast to some prior studies.

On the basis of the findings, the researchers suggest that smartphone use may inadvertently prolong toilet time, potentially increasing pressure in anal tissues, which may then lead to haemorrhoids.

This study could help inform clinicians’ recommendations to patients. Future research could also expand on these findings, such as by tracking patients over time and exploring interventions to limit prolonged smartphone use on the toilet. 

Trisha Pasricha, senior author of the study, adds: “Using a smartphone while on the toilet was linked to a 46 per cent increased chance of having haemorrhoids. We’re still uncovering the many ways smartphones and our modern way of life impact our health. It’s possible that how and where we use them – such as while in the bathroom –can have unintended consequences.

“This study bolsters advice to people in general to leave the smartphones outside the bathroom and to try to spend no more than a few minutes to have a bowel movement. If it’s taking longer, ask yourself why. Was it because having a bowel movement was really so difficult, or was it because my focus was elsewhere?

“It’s incredibly easy to lose track of time when we’re scrolling on our smartphones – popular apps are designed entirely for that purpose. But it’s possible that constantly sitting longer on the toilet than you intended because you’re distracted by your smartphone could increase your risk of haemorrhoids. We need to study this further, but it’s a safe suggestion to leave the smartphone outside the bathroom when you need to have a bowel movement.”

Provided by PLOS