Scientists develop new methods to detect Huntington's disease progression

A team of scientists in the UK developed non-invasive measurement techniques and novel analysis methods to decode disease progression and evaluate the effect of potential treatments or lifestyle changes in people with Huntington's disease.

Huntington's is a genetic disease where the brain’s nerve cells (neurons) gradually break down and die. The condition leads to dementia, with a progressive decline in an individual's movement, memory, and cognition. There is currently no cure.

The team from Lancaster University in the UK showed that Huntington's disease not only affects nerve cells in the brain but also has widespread effects on microscopic blood vessels.

The changes were also observed before symptoms of the disease appeared, demonstrating the potential for this research to predict brain health and evaluate the beneficial effects of lifestyle changes or treatments.

Professor Aneta Stefanovska of Lancaster University said that they hope that the novel method can help “monitor the disease progression and evaluate the effect of potential treatments or lifestyle changes” in people with “Huntington's and other neurodegenerative diseases.”

Professor Aneta added that the study would also lead to “new treatments of Huntington's disease targeting the vasculature and brain metabolism."

In their study, published in the journal Brain Communications, the team investigated changes in the coordination between neuronal activity and the brain's oxygenation in Huntington's disease.

They combined non-invasive measurement techniques and novel analysis methods -- probes emitting infrared light were placed on the heads of participants in the study.

Using infrared light, the researchers could measure the brain's blood oxygenation.

Further, using electrodes, which can measure electrical activity from neurons, the team studied the many rhythms related to brain and cardiovascular system functioning via mathematical techniques.

These rhythms included the heart and respiration rates, related to the transport of nutrients and oxygen, as well as slower rhythms associated with local control of blood flow.

The team explained that brain activity manifests in faster rhythms. Efficient functioning of the brain depends on how well all these rhythms are orchestrated.

https://www.newkerala.com/news/2024/33081.htm

Insomnia loss can raise risk of ovarian cancer, impact survival: Experts

Women with sleep loss condition insomnia may be at significant risk of developing ovarian cancer, said experts on Tuesday.

Insomnia is a common sleep disorder that can make it difficult for a person to fall asleep or stay asleep. People with the condition are also likely to wake up too early and not be able to get back to sleep. They may continue to feel tired after waking up.

“Insomnia, commonly linked to stress and anxiety, may also play a role in the risk and survival rates of ovarian cancer patients. Research suggests that disturbed sleep patterns could heighten inflammation and weaken the immune system, potentially fostering cancer growth,” Dr. Kinjal Kothari, Associate Consultant - Obstetrics and Gynecology, Manipal Hospital, Goa, told IANS.

A recent study published in the Lancet shows that treating insomnia in high-grade ovarian cancers can improve survival. The study also proposed that treating insomnia may be able to prevent ovarian cancer. Cancer incidence and prevalence are on a rising trend. With the trend, there is a blazing need to study the patterns of the disease and ways to improve the survival and quality of life of the patient.

“Sleep disorders are common among cancer patients. It may be a sleepless or abnormal sleep-wake cycle; probably more than half of the patients are affected. The patient's quality of life is negatively impacted,” Dr. Karthik K S, Consultant Surgical Oncology, KMC Hospital, Mangalore, told IANS.

Sleep symptoms may also be due to the psychological impact (like anxiety and depression) of the disease on the patient and the family, the doctor said. “Patients may have sleep loss because of pain and pressure symptoms of the cancer. Side effects and complications of treatment like nausea and vomiting can also affect sleep,” Dr. Karthik said.

Dr. M.A. Raja, Director & Senior Consultant - Medical Oncology, MGM Cancer Institute, Chennai told IANS that sleep disorders, such as insomnia, are known to increase the risk of breast and ovarian cancers and negatively affect their prognosis.

“Sleep is essential for the human body, intricately involved in endocrine, metabolic, and immunoregulatory pathways, which are also implicated in various cancers. These shared pathways may account for the increased risk of sleep disturbances among cancer patients, with insomnia being the most prevalent,” the doctor said.

Moreover, insomnia often leads to poorer mental health, which can indirectly affect treatment adherence and overall well-being during cancer therapy. Understanding this connection underscores the importance of addressing sleep disturbances in cancer care.

“Developing tailored interventions, such as cognitive behavioural therapy for insomnia, could potentially improve outcomes for ovarian cancer patients by promoting better sleep and bolstering resilience against the disease,” Dr. Kinjal said.

https://www.newkerala.com/news/2024/33292.htm

Study decodes how pathogens infect human lung tissue

A new study on Monday showed novel insights into how pathogens invade the lungs using lab-grown lung microtissues generated from human stem cells.

The team from the Biozentrum of the University of Basel in Switzerland focussed on Pseudomonas aeruginosa, part of WHO’s list of 12 of the world’s most dangerous bacterial pathogens.

The bacterium targets specific lung cells and has developed a sophisticated strategy to break through the lungs’ line of defence. It is especially threatening to immunocompromised patients and those on mechanical ventilation, with mortality rates up to 50 per cent.
In the journal Nature Microbiology, the team describes how Pseudomonas breaches the top layer of lung tissue and invades deeper areas by using lab-grown human lung microtissues that realistically mimic the infection process inside a patient’s body. "These lung models enabled us to uncover the pathogen’s infection strategy. It uses the mucus-producing goblet cells as Trojan horses to invade and cross the barrier tissue. By targeting the goblet cells, which make up only a small part of the lung mucosa, the bacteria can breach the defence line and open the gate," said Prof Urs Jenal at the Biozentrum.
Pseudomonas attacks and invades the goblet cells via secretion systems. It then replicates inside the cells and ultimately kills them. The burst of the dead cells leads to ruptures in the tissue layer, affecting the protective barrier. With this, the pathogens rapidly colonise and spread into deeper tissue regions.
Jenal’s team also developed a biosensor to measure and track a small signalling molecule called c-di-GMP in individual bacteria in real-time.https://www.newkerala.com/news/2024/33156.htm

Study finds new therapeutic targets to fight against type 2 diabetes

The fact that individuals with type 2 diabetes have elevated fasting glucose levels is among the most perplexing factors for them. This is due to the fact that in these insulin-resistant individuals, the liver produces glucose, a process that still raises many unanswered issues for scientists.

The most significant developments in our knowledge of this mechanism are now presented in a review paper that was published in the journal Trends in Endocrinology & Metabolism. In the battle against type 2 diabetes mellitus, which the World Health Organization (WHO) lists as one of the pandemics of the twenty-first century, it also aids in the discovery of novel therapeutic targets.

The UB Institute of Biomedicine (IBUB), the Sant Joan de Deu Research Institute (IRSJD), the Faculty of Pharmacy and Food Sciences at the University of Barcelona, the Centre for Biomedical Research Network on Diabetes and Associated Metabolic Diseases (CIBERDEM), and Professor Manuel Vazquez-Carrera are the study's leaders. Experts Emma Barroso, Javier Jurado-Aguilar, and Xavier Palomer (UB-IBUB-IRJSJD-CIBERDEM) as well as Professor Walter Wahli from the University of Lausanne (Switzerland) are involved in the work.

Type 2 diabetes mellitus is an increasingly common chronic disease that results in high levels of circulating glucose -- the cellular energy fuel -- due to a deficient insulin response in the body. It can cause severe organ damage and is estimated to be under-diagnosed in a high percentage of the affected population worldwide.

In patients, the glucose synthesis pathway in the liver (gluconeogenesis) is hyperactivated, a process that can be controlled by drugs such as metformin. "Recently, new factors involved in the control of hepatic gluconeogenesis have been identified. For example, a study by our group revealed that growth differentiation factor (GDF15) reduces the levels of proteins involved in hepatic gluconeogenesis", says Professor Manuel Vazquez-Carrera, from the UB's Department of Pharmacology, Toxicology and Therapeutic Chemistry.

To make progress in the fight against this pathology, it will also be necessary to further study pathways such as TGF-b, which is involved in the progression of metabolic dysfunction-associated fatty liver disease (MASLD), a very prevalent pathology that often coexists with type 2 diabetes mellitus. "TGF-b plays a very relevant role in the progression of liver fibrosis and has become one of the most important factors that may contribute to increased hepatic gluconeogenesis and, therefore, to type 2 diabetes mellitus. Therefore, studying the involvement of the TGF-b pathway in the regulation of hepatic gluconeogenesis could help to achieve better glycaemic control", stresses Vazquez-Carrera.

However, acting on a single factor to improve the regulation of gluconeogenesis does not seem to be a sufficient therapeutic strategy to adequately control the disease.

"It would be important to be able to design combination therapies that could consider the different factors involved to improve the approach to type 2 diabetes mellitus", Vazquez-Carrera says.

"Today there are several molecules -- TGF-b, TOX3, TOX4, etc. -- that could be considered therapeutic targets for designing future strategies to improve patients' well-being. Their efficacy and safety will determine their therapeutic success. We cannot lose sight of the fact that controlling the overactivation of hepatic gluconeogenesis in type 2 diabetes mellitus has an additional difficulty: it is a key pathway for making glucose available in fasting situations, it is finely modulated by numerous factors and this makes regulation difficult", he adds.

Interestingly, other factors involved in the control of gluconeogenesis have also been identified in patients hospitalised with COVID-19 who showed high glucose levels. "Hyperglycaemia was very prevalent in patients hospitalised with COVID-19, which seems to be related to the ability of SARS-CoV-2 to induce the activity of proteins involved in hepatic gluconeogenesis", the expert notes.

The mechanisms of action of metformin, the most commonly prescribed drug for the treatment of type 2 diabetes, which reduces hepatic gluconeogenesis, are still not fully understood. It has now been discovered that the drug decreases gluconeogenesis via inhibition of complex IV of the mitochondrial electron transport chain. This is a mechanism independent of the classical effects known until now through activation of the AMPK protein, a sensor of the cell's energy metabolism.

"Inhibition of mitochondrial complex IV activity by metformin -- not complex I as previously thought -- reduces the availability of substrates required for hepatic glucose synthesis", says Vazquez-Carrera.

In addition, metformin can also reduce gluconeogenesis through its effects on the gut, leading to changes that ultimately attenuate hepatic glucose production in the liver. "Thus, metformin increases glucose uptake and utilisation in the gut, and generates metabolites capable of inhibiting gluconeogenesis when they reach the liver via the portal vein. Finally, metformin also stimulates the secretion of GLP-1 in the intestine, a hepatic gluconeogenesis inhibitory peptide that contributes to its anti-diabetic effect", he explained.

https://www.newkerala.com/news/2024/32777.htm

Young, women more likely to suffer from multiple sclerosis: Experts

Young adults and women are more likely to suffer from multiple sclerosis, said experts on Saturday.

Multiple Sclerosis (MS) is a complex, chronic, autoimmune, and neurological disease that primarily affects the central nervous system, leading to a range of symptoms and health issues.

Data from the World Health Organisation (WHO) estimate that over 1.8 million people worldwide live with MS.

The prevalence of MS in India ranges from 7 to 30 per 100,000 people, according to various studies.

“MS can strike anyone at any age, however, persons between the ages of 20 and 40 are the ones who are diagnosed with it most frequently. Women are disproportionately affected since they are two to three times more likely than men to have the condition,” Dr. Himanshu Champaneri Senior Consultant- Department of Neurosciences and Neurosurgery, Marengo Asia Hospitals, Gurugram, told IANS.

Common symptoms include numbness or sensory loss, paraesthesia in limbs or face, vision loss, weakness in one or more limbs, double vision, imbalance while walking, and bladder problems such as difficulty holding or passing urine.

In addition, some patients experience a current-like sensation running down the spine with neck movements.

These symptoms typically develop over a few days to weeks, differentiating them from stroke symptoms, which have a rapid onset within seconds to minutes.

Dr Neeraj Balaini, Consultant – Neurology, Aster RV Hospital, told IANS that the exact cause of MS is not fully understood.

“Risk factors for MS include genetic predisposition, certain viral infections (such as Epstein-Barr virus and Human herpes virus-6), smoking, and vitamin D deficiency,” he said.

The doctor further explained that in MS, there is a loss of myelin -- the insulating covering around nerves in the brain and spinal cord.

This demyelination disrupts the electrical signals in the nerves, leading to the various symptoms of MS.

“Severe myelin damage can also result in the loss of nerve fibres themselves,” Dr. Neeraj said.

“MS is treatable but not curable. Without treatment, patients may accumulate disabilities from repeated attacks or enter a progressive phase where disability increases gradually without new attacks.

“Clinical depression is more frequent in people with MS due to both the psychological impact of the disease and potential neuroendocrine changes caused by MS,” he noted.

Along with medications, the experts stressed a balanced diet and healthy lifestyle to manage MS.

Eating a healthy and nutritious diet, managing weight, avoiding alcohol and tobacco, maintaining a balanced diet, ensuring good sleep hygiene, and managing hypertension and diabetes, can help preserve healthy neurons and support overall health.

Physical exercise is also important in managing MS and improving quality of life.

In addition, “taking preventative measures to avoid infections may be helpful as some viral infections are known to trigger MS and genetic counselling may be helpful for those with a family history of the disease,” Dr. Himanshu said.

https://www.newkerala.com/news/2024/32809.htm

Study gives more insight into type 2 diabetes

Having high fasting glucose levels is one of the most perplexing characteristics of type 2 diabetes mellitus patients. This is because the liver produces glucose in these insulin-resistant people, a mechanism that still raises many unanswered issues for scientists.

An extensive summary of the most significant developments in comprehending this process is now provided in a review paper that was published in the journal Trends in Endocrinology & Metabolism.

Additionally, it aids in the discovery of novel therapeutic targets in the battle against type 2 diabetes mellitus, which the World Health Organization (WHO) lists as one of the pandemics of the twenty-first century.

The study is led by Professor Manuel Vazquez-Carrera, from the Faculty of Pharmacy and Food Sciences of the University of Barcelona, the UB Institute of Biomedicine (IBUB), the Sant Joan de Deu Research Institute (IRSJD) and the Centre for Biomedical Research Network on Diabetes and Associated Metabolic Diseases (CIBERDEM). Among the participants in the study are the experts Emma Barroso, Javier Jurado-Aguilar and Xavier Palomer (UB-IBUB-IRJSJD-CIBERDEM) and Professor Walter Wahli, from the University of Lausanne (Switzerland).

Therapeutic targets to fight the disease

Type 2 diabetes mellitus is an increasingly common chronic disease that results in high levels of circulating glucose -- the cellular energy fuel -- due to a deficient insulin response in the body. It can cause severe organ damage and is estimated to be under-diagnosed in a high percentage of the affected population worldwide.

In patients, the glucose synthesis pathway in the liver (gluconeogenesis) is hyperactivated, a process that can be controlled by drugs such as metformin. "Recently, new factors involved in the control of hepatic gluconeogenesis have been identified. For example, a study by our group revealed that growth differentiation factor (GDF15) reduces the levels of proteins involved in hepatic gluconeogenesis", said Professor Manuel Vazquez-Carrera, from the UB's Department of Pharmacology, Toxicology and Therapeutic Chemistry.

To make progress in the fight against this pathology, it will also be necessary to further study pathways such as TGF-b, which is involved in the progression of metabolic dysfunction-associated fatty liver disease (MASLD), a very prevalent pathology that often coexists with type 2 diabetes mellitus. "TGF-b plays a very relevant role in the progression of liver fibrosis and has become one of the most important factors that may contribute to increased hepatic gluconeogenesis and, therefore, to type 2 diabetes mellitus. Therefore, studying the involvement of the TGF-b pathway in the regulation of hepatic gluconeogenesis could help to achieve better glycaemic control", stresses Vazquez-Carrera.

However, acting on a single factor to improve the regulation of gluconeogenesis does not seem to be a sufficient therapeutic strategy to adequately control the disease.

"It would be important to be able to design combination therapies that could consider the different factors involved to improve the approach to type 2 diabetes mellitus", Vazquez-Carrera said.

"Today there are several molecules -- TGF-b, TOX3, TOX4, etc. -- that could be considered therapeutic targets for designing future strategies to improve patients' well-being. Their efficacy and safety will determine their therapeutic success. We cannot lose sight of the fact that controlling the overactivation of hepatic gluconeogenesis in type 2 diabetes mellitus has an additional difficulty: it is a key pathway for making glucose available in fasting situations, it is finely modulated by numerous factors and this makes regulation difficult", he adds.

Interestingly, other factors involved in the control of gluconeogenesis have also been identified in patients hospitalised with COVID-19 who showed high glucose levels. "Hyperglycaemia was very prevalent in patients hospitalised with COVID-19, which seems to be related to the ability of SARS-CoV-2 to induce the activity of proteins involved in hepatic gluconeogenesis", the expert notes.

Metformin: the unknowns of the most prescribed drug

The mechanisms of action of metformin, the most commonly prescribed drug for the treatment of type 2 diabetes, which reduces hepatic gluconeogenesis, are still not fully understood. It has now been discovered that the drug decreases gluconeogenesis via inhibition of complex IV of the mitochondrial electron transport chain. This is a mechanism independent of the classical effects known until now through activation of the AMPK protein, a sensor of the cell's energy metabolism.

"Inhibition of mitochondrial complex IV activity by metformin -- not complex I as previously thought -- reduces the availability of substrates required for hepatic glucose synthesis", said Vazquez-Carrera.

In addition, metformin can also reduce gluconeogenesis through its effects on the gut, leading to changes that ultimately attenuate hepatic glucose production in the liver. "Thus, metformin increases glucose uptake and utilisation in the gut, and generates metabolites capable of inhibiting gluconeogenesis when they reach the liver via the portal vein. Finally, metformin also stimulates the secretion of GLP-1 in the intestine, a hepatic gluconeogenesis inhibitory peptide that contributes to its anti-diabetic effect", he explained.

https://www.newkerala.com/news/2024/33053.htm

Can statins help prevent cancer? New study offers clues

A new study suggests that statin therapy could help prevent inflammatory-related cancers, particularly pancreatic cancer.

• Statin medications help keep cholesterol levels within a healthy range, but researchers are interested in other uses for these medications.
• Inflammation is one risk factor for certain types of cancer, such as pancreatic cancer.
• A recent study found that using the statin pitavastatin may assist in blocking a particular protein’s action to suppress chronic inflammation.
• The findings suggest that statin therapy could potentially prevent inflammatory-related cancers, particularly pancreatic cancer.

Cancer prevention is a major field of research, and experts are continuing to learn more about what factors may contribute to cancer development.

One area of interest is how chronic inflammation in certain areas of the body may contribute to cancer risk.

A recent study published in Nature Communications examined some of the pathways involved in developing chronic inflammation.

The results suggest the statin drug pitavastatin could help suppress chronic inflammation and prevent pancreatic cancer development. If future research confirms the findings, this drug could be a preventive measure in clinical practice.

What are statins used for?

Statins are typically prescribed to help lower cholesterol levels in people whose “bad” cholesterol levels are too high.

Statins can be used in combination with lifestyle changes to help keep cholesterol in a healthy range. For example, people may minimize their saturated fat intake and increase their physical activity levels.

Non-study author Dr. Robert Salazar, a cardiologist with Memorial Hermann, explained the following to Medical News Today:

“Statins are typically used to manage high cholesterol in patients at elevated risk for atherosclerotic cardiovascular disease (ASCVD.) Generally speaking, a statin is started when a patient’s individual risk of heart attacks, strokes or peripheral arterial disease is high. Statin medications are also started when measured blood cholesterol levels are high or after a stroke or heart attack. The effectiveness of statin drugs is then checked using a follow up blood cholesterol level to ensure an adequate response.”

Alternative uses for statins for other health conditions are an ongoing area of research.

Effects of statins on inflammation, cancer

Researchers of the current study note that chronic inflammation contributes to cancer development.

Several inflammatory conditions contribute to an increased cancer risk. For example, chronic pancreatitis (an inflammation of the pancreas) raises the risk of pancreatic cancer.

The researchers of the current study note that interleukin 33 (IL-33) is one protein that helps initiate cancer-prone chronic inflammation. They wanted to understand more about the underlying mechanisms involved in this relationship and whether there was a way to alter it.

Researchers utilized mice, human tissue samples, and cell lines. They induced chronic inflammation in mice on the skin and in the pancreas. They found that IL-33 was highly expressed in the inflamed skin and pancreas.

Based on further analysis, they identified that inflammation induction activated a specific signaling pathway called TLR3/4, suggesting that this pathway may cause the IL-33 expression that occurs in chronic inflammation. They further identified another cellular mechanism, TBK1-IRF3, regulating IL-33 expression in chronic pancreatitis and dermatitis in mice.

Researchers then tested the use of pitavastatin to block IL-33 expression. Their work suggests that pitavastatin may successfully block IL-33 expression and, thus, the related chronic pancreatitis.

While looking at human tissue samples, they further confirmed that the IRF3-IL-33 signaling axis is active when the pancreas is inflamed and in cases of pancreatic cancer.

Finally, researchers looked at electronic health records from over 200 million people to look at the use of pitavastatin and the risk for pancreatic cancer. Researchers found that people taking pitavastatin were at a decreased risk for chronic pancreatitis and pancreatic cancer.

Study author Shadmehr Demehri, MD, PhD, explained the key findings of the research to MNT:

“15–20% cancer death worldwide relate to cancers that develop in the context of chronic inflammation. We set out to determine what factor initiates the development of chronic inflammation in various organs. Based on our discovery that an immune factor, called interleukin 33, is the driver of cancer-prone chronic inflammation, we investigated the cellular mechanism that regulates the expression of this immune factor. Our findings, reported in the current publication, reveal this mechanism and demonstrate how [a] statin drug can block this immune factor expression in experimental models and prevent chronic inflammation and cancer in them. Interestingly, we find statin use by patients (to treat high cholesterol) associates with reduced risk of pancreatitis (inflammation of pancreas) and reduced risk of pancreatic cancer.”

The study demonstrates another potential use for statins in the future. Salazar noted the following:

“This study and its findings are quite compelling in demonstrating additional benefits from statin drugs that are independent of cholesterol levels. In particular, lowering inflammation further protects patients from negative outcomes including heart attacks, strokes, dementia, autoimmune disease, premature aging and cancer.”

More studies on statins and cancer prevention needed

This preliminary research requires more research before these concepts can reach practical clinical application.

Since it relied on components like mouse models, it’s not perfectly clear how the data applies to humans. The research from patient health records was also from North America and Europe, so more diversity may be needed in this research area.

“It is critical to examine statin efficacy for cancer prevention in chronic inflammation directly in patients through clinical trials,” Demehri said.

“We also aim to extend our work to encompass the array of chronic inflammatory diseases that render patients prone to cancer (e.g., ulcerative colitis and hepatitis) to help prevent cancer in all patients affected by chronic inflammation.”

If future research continues to confirm the findings, it could benefit clinical practice. Non-study author Anton Bilchik, MD, PhD, surgical oncologist, chief of medicine, and director of the Gastrointestinal and Hepatobiliary Program at Providence Saint John’s Cancer Institute in Santa Monica, CA, noted the following to MNT:

“The findings are very provocative because pancreas cancer is a deadly cancer with limited treatment options. If the anti-inflammatory effect of statins can reduce the chance of developing pancreas cancer particularly in high risk patients this will be practice changing and play an important role not only in reducing the risk of heart attacks but also in cancer prevention.”

https://www.medicalnewstoday.com/articles/can-statins-help-prevent-cancer#What-are-statins-used-for?

Synthetic estrogens used in birth control pills linked to anxiety in rats

The synthetic hormones in birth control pills may affect mental health, research suggests.

• The combined hormonal contraceptive pill is the second most popular form of contraception in the United States, besides condoms.
• Ethinyl estradiol has been used in the contraceptive pill since it was first created 60 years ago.
• Researchers have discovered that rats given this hormone exhibited more behaviors associated with anxiety, compared to a more natural estrogen used in a more modern form of the contraceptive pill.

Rats given synthetic estrogens used in birth control pills exhibited greater signs of anxiety than those given natural estrogens, researchers have found.

The study showed that synthetic estrogens were associated with higher sex hormone-binding globulin and lower steroid hormone levels when compared to natural ones. The researchers showcased their results at ENDO 2024, the Endocrine Society’s annual meeting in Boston, M.A., which was presented by a master’s student at Midwestern University.

The natural estrogen used in this study was similar to the one used in the formulation for the NOMAC-E2 Combined Oral Contraceptive, known as Zoely, and produced by the pharmaceutical company Merck. The synthetic estrogen used in most combined hormonal contraceptive pills on the market is a highly potent synthetic estrogen called ethinyl estradiol.

Researchers had been looking for natural estrogen to use in combined hormonal contraceptive pills since its inception 60 years ago, but these had not been potent enough for those pills to be an effective form of hormonal contraceptive. This changed in 2011 when Zoely was introduced to the market.

Abigail Hegwood, M.S., a P.h.D. candidate who carried out the study, said she had wanted to investigate the new, natural estrogen on the market as she had become aware there was little epidemiological data on the side effects of specific progestins and estrogens.

“Really I wanted to know [whether there is] a difference between these two estrogens. They just released this natural estrogen on the market. Does this possibly give us an opportunity to find a difference between formulations in terms of behavioral side effects?” she said.

She now plans on submitting the results of this research for peer review in the coming months.

Different behavior with synthetic estrogen

Three groups of 12 female rats were given either ethinyl estradiol a synthetic estrogen with dienogest, a progestin often combined with it in oral combined hormonal contraception, or estradiol valerate a natural estrogen with dienogest, or a control, delivered via a subcutaneous pump for 28 days. The researchers tested the rats’ spatial awareness and anxiety in a maze test, between days 20-28, and collected serum samples on day 28.

The researchers discovered that the rats had similar spatial memory across all three groups. However, those who were given the synthetic estrogen had a different response to the spatial memory task in the maze test, which is believed to be associated with anxiety-like behaviors in rats.

Serum samples also showed that both types of estrogen reduced circulating testosterone.

The authors note levels of the type of estradiol made in the ovaries were below the detection limit in over half of rats given ethinyl estradiol.

How estrogen is linked to spatial memory and anxiety

Previous research has shown that higher levels of testosterone and E2 reduce anxiety-related behaviors and improve spatial memory, authors noted. They propose that the results they have seen are due to the effect of synthetic estrogens on the brain.

“Ethinyl estradiol and estradiol valerate have different effects on hormone-binding globulin. And hormone-binding globulin can bind and render steroid hormones in the blood unavailable for use by the body. And so we know that ethinyl estradiol increases hormone-binding globulin, which increases the amount of bound steroid hormone in the blood,” said Hegwood.

“So my hypothesis would be that because ethinyl estradiol is having this greater effect on the availability of steroid hormones, it would have a greater effect on the actions that these steroid hormones have on the body, including the brain,” she added.

Her supervisor Alesia Prakapenka, Ph.D., an assistant professor in the Biomedical Sciences program at Midwestern University in Downers Grove, Ill, told Medical News Today:

“Another potential outcome is there’s the feedback loop that’s being halted by the contraceptive treatments between the hypothalamus, the pituitary, and the gonads.”

Naturally-produced circulating estrogen was below the level of detection in many of the rats given ethinyl estradiol.

“What we actually saw is that with the synthetic ethinyl estradiol group, more than half of the samples in that group had 17-beta estradiol levels that were actually below the limit of detection. And so it could be that even if it’s not the hormone itself from the contraceptive, it may be changing something within the feedback loop that then could be having that effect,” explained Prakapenka.

Prakapenka said there hasn’t been much focus on the behavioral effects of hormonal contraception.

“I think bringing this to attention is exciting because now we can start to look at it more and then combine it with additional factors that are across the lifespan could be impacting females, including pregnancy, including menopause,” she said.

TAILORED BIRTH CONTROL OPTIONS

“There’s a lot of development that’s happening with different options for menopausal hormone therapy. So maybe taking those strategies, applying them to contraceptive use as well, kind of across the board, what a female can go through and how we can inform them of this. These are your options. These are kind of the individual changes that you may experience and how to adjust based on that individual woman, as opposed to women as a whole or females as a whole.”— Alesia Prakapenka, Ph.D.

How hormonal contraception affects behavior

While it was possible that combined hormonal contraception could have an effect on the brain and therefore behavior, it was likely that this effect would be small, said Professor Jonathan Schaffir, MD, and Vice Chair of Education in the Department of Obstetrics and Gynecology at the Ohio State University College of Medicine, who was not involved in the research.

“There are receptors for estrogens as well as other steroids in the human brain, and that, you know, we know that providing exogenous hormones can influence mood and behavior to some degree. That said, I think that the influence of oral contraceptives is usually small and it’s a small percentage of women who have any significant side effects that affect mood,” he told Medical News Today in an interview.

https://www.medicalnewstoday.com/articles/synthetic-estrogens-birth-control-pills-linked-anxiety-rats#How-hormonal-contraception-affects-behavior

Sugar substitute xylitol linked to higher risk of heart attack, stroke

Experts say there are a number of health concerns with artificial sweeteners.

• Xyltol is a sugar alcohol added to many products, ranging from sugar-free candy and gum to toothpaste.
• Researchers say high levels of circulating xylitol are associated with an elevated three-year risk of cardiovascular events.
• They noted their study had several limitations, including clinical observation studies demonstrate association and not causation.

An artificial sweetener known as sugar alcohol has never sounded like the healthiest thing for people. Turns out, it may not be.

In a study published in the European Heart Journal, Cleveland Clinic researchers report that higher amounts of xylitol, a type of sugar alcohol, can increase risk of heart attack, stroke, and other cardiovascular events.

The researchers said they found the associations in a large-scale patient analysis, a clinical intervention study, and preclinical research models.

Xylitol is a lower-calorie sugar substitute with a low glycemic index. Sugar alcohols are carbohydrates that don’t actually contain alcohol.

Xylitol occurs naturally in small amounts in fibrous fruits and vegetables, corn cobs, trees, and the human body. It’s used as a sugar substitute because its taste is comparable to sugar but has fewer calories.

Xylitol is found in many products, ranging from sugar-free candy and gum to toothpaste. People also use it as a sweetener and for baking.

Sugar alcohol and cardiovascular risks

The research team said over the past decade, sugar substitutes such as sugar alcohols and artificial sweeteners have significantly increased in processed foods promoted as healthy alternatives.

The Cleveland Clinic team found a similar link between another sugar alcohol, erythritol, and cardiovascular risk last year. They said in a statement that xylitol isn’t as common as erythritol in keto or sugar-free products in the United States, but they noted it is common in other countries.

“This study again shows the immediate need for investigating sugar alcohols and artificial sweeteners, especially as they continue to be recommended in combating conditions like obesity or diabetes,” said Dr. Stanley Hazen, the chairperson of Cardiovascular and Metabolic Sciences at Cleveland Clinic’s Lerner Research Institute as well as the co-section head of preventive cardiology in the Heart, Vascular and Thoracic Institute, in the statement.

“It does not mean throw out your toothpaste if it has xylitol in it, but we should be aware that consumption of a product containing high levels could increase the risk of blood clot related events,” Hazen added.

Details on the study of xylitol and heart health

In an analysis of more than 3,000 subjects in the United States and Europe, the researchers reported that high levels of circulating xylitol were associated with an elevated three-year risk of cardiovascular events.

A third of subjects with the highest amount of xylitol in their plasma were found more likely to experience a cardiovascular event.

The team conducted pre-clinical testing to confirm the findings. They discovered xylitol caused clotting in platelets and heightened risk of thrombosis.

The researchers also tracked platelet activity from subjects who ingested a xylitol-sweetened drink versus a glucose-sweetened drink. They found every measure of clotting ability significantly increased immediately following ingestion of xylitol but not glucose.

The team said the study had several limitations, including that clinical observation studies demonstrate association and not causation. They said more studies are needed to assess the long-term cardiovascular safety of xylitol.

What experts think about artificial sweeteners

Dr. Cheng-Han Chen, an interventional cardiologist and medical director of the structural heart program at MemorialCare Saddleback Medical Center in California, told Medical News Today that people should consider avoiding large amounts of xylitol until its effects are better understood.

“Based on this study, it is thought that xylitol affects the ‘stickiness’ of platelets in the bloodstream, potentially increasing the risk of forming a blood clot in the heart or in the brain,” said Chen, who was not involved in the research.

Dr. Rigved Tadwalkar, a consultative cardiologist at Providence Saint John’s Health Center in California, told Medical News Today it’s important to remember the study was observational and doesn’t definitively prove xylitol directly causes cardiovascular problems.

“However, the findings raise enough concern to warrant further investigation,” Tadwalkar, who was not involved in the research, said. “This new study adds another chapter to the evolving story of sugar substitutes and heart health. In recent years, there has been a growing awareness that these alternatives might not be as risk-free as once believed.”

Tadwalkar added it’s also important to note erythritol is more prominent in the United States within keto and sugar-free products, whereas xylitol finds wider use in other countries as well as in some sugar-free candies and chewing gums.

“This new research prompts consideration of the long-term cardiovascular safety of various sugar substitutes,” Tadwalkar said. “This new study on xylitol has significant implications for both consumers and healthcare professionals.”

He added that xylitol may have this impact on the heart because, according to the study, xylitol may increase platelet activity and enhance blood clot formation.

“This heightened activity could raise the risk of clots forming unexpectedly, potentially leading to cardiovascular events like heart attack or stroke,” Tadwalkar said. “It is important to note, however, that this is ultimately just a theory. More research is needed to definitively understand the exact biological processes at play.

Health effects of sugar substitutes

Dr. Bradley Serwer, a cardiologist and chief medical officer at VitalSolution, which provides cardiovascular and anesthesiology services to hospitals nationwide, told Medical News Today that problems with sugar substitutes go back more than a century.

“Saccharin was first discovered in 1879 and widely introduced as an artificial sweetener in the early 20th century,” Serwer said. “There was notable concern that saccharin could cause cancer in the 1970s, but this was later clarified in the early 2000s when the National Toxicology Program removed saccharin from its list of potential carcinogens.

Serwer said the health value of sugar substitutes depends on someone’s medical conditions.

“Ideally, one would avoid them altogether and maintain a healthy balanced diet with a low glycemic index,” said Serwer, who was not involved in the research. “I would encourage patients to consider their desire for sweets over their overall health. The natural options such as monk fruit extract may be reasonable.”

“Take caution. Even products such as Stevia, which is derived from the Stevia rebaudiana plant, is mixed with erythritol, which may also increase the risk of platelet clumping and was associated with higher cardiovascular events,” he added.

https://www.medicalnewstoday.com/articles/sugar-substitute-xylitol-linked-to-higher-risk-of-heart-attack-stroke#Health-effects-of-sugar-substitutes