Tag: 27/9/23

Categories : Cardiovascular Disease Obstetrics & GynaecologyTags : Leave a comment

Study Links Hot Flashes to Cardiovascular Risk Factors

On By ModernMedia
Photo by CDC on Unsplash

It has long been known that hot flashes are linked to a number of adverse health effects. Emerging data suggests an association between them and cardiovascular disease. A new study is the first to link physiologically assessed hot flashes with heightened systemic inflammation – a risk factor for cardiac disease. Study results will be presented during the 2023 Annual Meeting of The Menopause Society in Philadelphia September 27-30.

Vasomotor symptoms, more often referred to as hot flashes, are one of the most common symptoms identified during the menopause transition, with roughly 70% of midlife women reporting them. Not only do they interfere with a woman’s quality of life, but they have also been related to physical health risks, such as cardiovascular disease.

Previous research linking hot flashes with heightened systemic inflammation has relied on self-reporting to document the frequency and severity of the hot flashes. These self-reports of hot flashes are limited as they ask women to recall hot flashes over weeks or longer and may be subject to memory or reporting biases. A new study that included 276 participants from the MsHeart study, however, utilised sternal skin conductance to physiologically assess hot flashes and tested whether more frequent physiologically assessed hot flashes are associated with heightened system inflammation.

While large increases in inflammatory markers indicate acute infection or clinical disease, small and sustained increases of markers of inflammation that are in the physiologically normal range are predictive of later disease risk. For example, small and/or sustained increases in inflammatory biomarkers (conceptualised as heightened levels of systemic inflammation) have been related to plaque development and atherosclerotic cardiovascular disease.

Based on the results, the researchers concluded that physiologically assessed hot flashes during wake were associated with higher levels of a high-sensitivity C-reactive protein, even after adjusting for potential explanatory factors such as age, education, race/ethnicity, body mass index, and oestradiol.

The results will be presented during the Annual Meeting of The Menopause Society as part of the presentation entitled “Physiologically measured vasomotor symptoms and systemic inflammation among midlife women.”

“This is the first study to examine physiologically measured hot flashes in relation to inflammation and adds evidence to a growing body of literature suggesting that hot flashes may signify underlying vascular risk and indicate women who warrant focused cardiovascular disease prevention efforts,” says Mary Carson, MS, lead author from the Department of Psychology at the University of Pittsburgh.

“Since heart disease is the leading cause of death for women in the US, studies like these are especially valuable,” adds Dr Stephanie Faubion, medical director of The Menopause Society. “Healthcare professionals need to ask their patients about their hot flash experiences as they not only interfere with their quality of life but may also indicate other risk factors.”

Source: EurekAlert!

Categories : Medical Research & TechnologyTags : Leave a comment

The Vagus Nerve also Plays a ‘Fight or Flight’ Role for the Heart

On By ModernMedia
Photo by Stephen Andrews

Researchers have reported in Circulation that the vagus nerve, known for its parasympathetic role in ‘resting and digesting’, also has an important role in exercise, helping the heart pump blood.

Exercise science currently holds that the ‘fight or flight’ (sympathetic) nervous system is active during exercise, helping the heart beat harder, and the ‘rest and digest’ (parasympathetic) nervous system is lowered or inactive. However, University of Auckland physiology Associate Professor Rohit Ramchandra says that this current understanding is based on indirect estimates and a number of assumptions which this new study has proven to be wrong.

“Our study finds the activity in these ‘rest and digest’ vagal nerves actually increases during exercise,” Dr Ramchandra says. “Our group has used ‘tour de force’ electrical recording techniques to directly monitor vagal nerve activity in exercising sheep and has found the activity in these vagal nerves going to the heart increases during exercise.

”For the heart to sustain a high level of pumping, it needs a greater blood flow during exercise to fuel the increased work it is doing: our data indicate that the increase in vagal activity does just this.”

During exercise, there is a four to five-fold increase in the amount of blood pumped out by the heart per minute, requiring increased cardiac output. This is modulated by autonomic nerves that travel from the brain, including the sympathetic and parasympathetic vagal nerves.

The vagal nerve connects the brain to the heart, and other internal organs including the gut, regulating the ‘rest and digest’ parasympathetic nervous system responses. The new research finds the parasympathetic and sympathetic nervous systems work together in exercise to help increase cardiac output. The researchers also investigated the role of mediators released by the cardiac vagal nerve.

“The cardiac vagus nerve releases multiple mediators, and previous research has focused on a neurotransmitter, acetylcholine, which has no impact on our ability to exercise,” says Dr Ramchandra. “Our study focused on a different mediator, vasoactive intestinal peptide (VIP) and it shows that the vagus nerve releases this peptide during exercise, which helps the coronary vessels dilate allowing more blood to pump through the heart.”

The first and co-corresponding author Dr Julia Shanks says, “Vasoactive intestinal peptide was first found in the gut and it does help in digestion, but what we now know is that it is also important in exercise.”

The trial was conducted in sheep, because of their similarity to humans in many important respects including cardiac anatomy and physiology. They are also well-established as an animal model to assist with finding ways to combat heart disease that translate to humans.

These fundamental findings could have applications in diseases, including heart failure, where people cannot tolerate exercise.

“This inability to carry out simple tasks involving exertion means that quality of life is severely compromised in these patients,” Dr Ramchandra says. “One potential reason why exercise tolerance is reduced is that the diseased heart simply does not receive enough blood. Our follow-up study will try to see whether we can use this important role of cardiac vagal nerves to improve exercise tolerance in heart failure.”

There is a lot of interest in trying to ‘hack’ or improve vagal tone as a means to reduce anxiety. Investigating this was outside the scope of the current study.

Dr Ramchandra says we do know that the vagus mediates the slowing down of heart rate and if we have high vagal activity, then our hearts should beat slower.

“Whether this is the same as relaxation, I am not sure, but we can say that regular exercise can improve vagal activity and has beneficial effects.”

Source: University of Auckland

Categories : HIVTags : Leave a comment

An Injectable Hydrogel could Deliver Long-term ART for HIV Patients

On By ModernMedia
Photo by Raghavendra V Konkathi on Unsplash

A new injectable solution that self-assembles into a gel under the right conditions could help manage HIV unlike any currently available methods, researchers report in the Journal of the American Chemical Society. Developed by John Hopkins University researchers, the new gel releases a steady dose of the antiretroviral lamivudine over six weeks, suggesting people living with HIV could have an alternative to the daily pill regimen.

“The primary challenge in HIV treatment is the need for lifelong management of the virus, and one way to address this is to reduce dosing frequencies to help patients stick to medical regimens,” said lead researcher Honggang Cui, a chemical and biomolecular engineer. “This new molecular design shows us a future in which drug hydrogelation can do that to improve HIV treatment.”

In plasma-like conditions, Cui’s team showed the gel quickly separates into molecules of lamivudine. By injecting the gel in the backs of mice, the researchers found one injection was sufficient to maintain effective and lasting drug concentrations for 42 days with nearly no side effects.

“Our goal is to help improve people’s quality of life,” Cui said. “The antiviral substance can be injected under the skin and remain in place over an extended period, releasing the therapeutic compound slowly and consistently – a critical need for individuals with HIV.”

For people living with HIV, the key is maintaining bloodstream drug levels at concentrations that suppress virus load in the body. But that can be difficult with traditional approaches because the body naturally rids itself of these chemicals, Cui said, which is why different treatments require different dosages and dosing frequencies to work.

Most antiretroviral therapies use a combination of drugs, so the researchers plan to include other drugs in tests. Because lamivudine is an FDA-approved drug to treat HIV and hepatitis B, the researchers said the hydrogel could also help manage hepatitis B.

“This is a novel way to deliver anti-HIV meds, and this platform has the advantage that a single polymer can be programmed to deliver several different drugs simultaneously,” said co-author Charles W. Flexner, a professor of medicine, pharmacology, and molecular sciences in the Johns Hopkins School of Medicine. “One of the drawbacks of the approved injectable HIV treatments is that none have activity against hepatitis B virus, which is a common co-infection with HIV, especially in Asia and Africa. This formulation delivers lamivudine, a drug active against both HIV and HBV, but can also be modified to deliver tenofovir, which is the current standard of care for HBV treatment.”

The team envisions their hydrogel working as a preventive measure, similar to how some people take anti-HIV drugs to avoid infection.

“Keeping the high drug levels in plasma for 42 days is very impressive,” Cui said. “But in the future, we hope it will be even longer.”

Hydrogels have unique water-absorbing properties that give them a jellylike consistency resembling biological tissue. The new gel undergoes self-formulation, stays close to the site of injection, and separates into molecules that can fend off the virus without the need for additional carriers or delivery materials.

“The most exciting aspect of these gel filaments is that they consist entirely of the therapeutic agent itself,” Cui said. “Everything originates from the same compound after injection, and this simplest drug formulation could streamline the regulatory approval process once clinical efficacy is demonstrated.”

The team tweaked the molecular properties of lamivudine to act as the building blocks of a supramolecular polymer, a large chain of repeating molecules that can either stick together tightly or come apart, depending on temperature, pH, and other external conditions.

Source: Johns Hopkins University

Categories : Metabolic DisordersTags : Leave a comment

Researchers Find a Mechanistic Link between Zinc Levels and Risk of Diabetes

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Researchers have identified a mechanistic link between zinc levels in humans and the risk of type 2 diabetes and non-alcoholic fatty liver disease (NAFLD). The research, published today as a Reviewed Preprint in eLife, is described by editors as a fundamental study that substantially advances our understanding of the role of zinc in metabolism. The evidence comes from genetic analysis of a large population of human participants and comprehensive lab studies of a potential therapeutic target for NAFLD and type 2 diabetes.

Converging lines of evidence have shown that zinc plays a crucial role in insulin production and glucose metabolism. “We know that increasing zinc intake improves blood glucose control in people with prediabetes or type 2 diabetes, and people with a mutation in a key zinc transporter protein have reduced risk of diabetes.” says first author Shek Man Chim, Principal Scientist at Regeneron Pharmaceuticals, Inc, New York, US. “However, the mechanism for how zinc influences systemic blood glucose levels and diabetes risk remains unclear.”

To explore the diabetes-protective role of zinc, Chim and colleagues tested loss-of-function mutations from genetic sequence data collected from a large population of participants of European ancestry who took part in the Regeneron Genetics Center-Geisinger Health System DiscovEHR study. This identified a rare mutation that causes loss of function in a zinc transporter protein called SLC39A5, associated with increased circulating zinc levels.

To confirm this, they looked at how loss-of-function mutations in SLC39A5 were associated with type 2 diabetes in a meta-analysis of four multi-ethnic European and US studies totalling >62 000 cases of diabetes and > 518 000 healthy controls. This confirmed that circulating zinc levels in carriers of the SLC39A5 loss-of-function mutation were elevated and associated with a reduced risk of diabetes.

Having identified SLC39A5 as an important clinical link between zinc and diabetes, the team explored its function by genetically deleting the zinc transporter protein in mice. As anticipated, these mice had elevated blood and tissue levels of zinc. When the team fed mice a high-fat, high-fructose diet to induce obesity, there was a significant reduction in fasting glucose compared to the control mice fed the same diet. Similar results were observed in a congenital (leptin receptor-deficiency) model of obesity. Loss of SLC39A5 also resulted in reduced insulin resistance.

As diabetes often coincides with NAFLD, the team explored whether loss of SLC39A5 protects the liver, too. As hoped, mice lacking SLC39A5 had less build-up of fat in the liver and in blood markers of liver damage. Moreover, mice lacking SLC39A5 but fed a high-fat, high-fructose diet also had less fat accumulation in the liver and improved insulin sensitivity compared to control mice.

The improvements seen in the livers of mice lacking SLC39A5 prompted the researchers to see whether loss of SLC39A5 protects against progression of non-alcoholic fatty liver disease to non-alcoholic steatohepatitis (NASH), a more severe liver inflammation that leads to fibrosis. They used a high-fat, high-cholesterol diet to induce NASH in mice and found increased markers of liver damage, body weight, fasting blood glucose and liver fibrosis. By contrast, the mice lacking SLC39A5 had reduced liver damage markers, fasting blood glucose and improvements in liver inflammation and fibrosis.

One concern highlighted by public reviewers was that observed differences in the metabolic consequences of SLC39A5 inactivation between male and female mice remained unclear. Further work will need to explore this further, as well as characterise the role of SLC39A5 in pancreatic cell function and glucose tolerance more fully.

“Our study provides for the first-time genetic evidence demonstrating the protective role of zinc against high blood sugar and unravels the mechanistic basis underlying this effect,” concludes senior author Harikiran Nistala, currently Head of functional Genomics at Alkermes Inc, Waltham, US. “Our observations suggest that blocking SLC39A5 could be a potential therapeutic avenue for type 2 diabetes and other indications where zinc supplementation alone is inadequate.”

Source: eLife

Categories : Emergency Medicine Healthcare Politics and RegulationsTags : Leave a comment

Alarm Raised over Amendments to Road Accident Fund Act

On By ModernMedia
Photo by Pixabay

By Tania Broughton for GroundUp

The Law Society of South Africa (LSSA) has urged members of the public and civic associations to formally object to proposed amendments to the Road Accident Fund Act which, if approved, will have “dire consequences” for all South African road users.

The draft amendment bill was gazetted earlier this month by the transport minister. It proposes major changes to how the fund operates and how it will pay claims.

According to the LSSA, it proposes significant changes to the existing law, including removing the rights of drivers, passengers and pedestrians to claim compensation for injuries they have suffered. Instead, it proposes that the fund will only provide significantly reduced “social benefits”.

And, says the LSSA, an innocent injured party would still be denied the common law claim against the guilty party for the balance of his or her loss.

Yet all road users contribute directly or indirectly to the fund through the fuel levy, estimated to be about R45-billion a year.

“The poor and disempowered, who make up the vast majority of claimants and who are compelled to use public transport, will bear the brunt of the consequences of these amendments. They will be forced into the public health system, as the prescribed tariffs will not cover the actual costs incurred at a private hospital. Under the present system, many receive treatment at dedicated private healthcare facilities,” the LSSA says in its statement.

Claimants will also not receive any lump sum payments and, if they are not able to produce a payslip, it was unlikely that they would receive compensation for loss of earnings.

The LSSA said those who can afford it will be compelled to take out private accident cover for medical and other expenses as well as accident benefits.

“This is likely to be very costly, as there will be no reimbursement of expenses covered from the fund. Medical aids will more than likely exclude cover or the cost thereof will have to materially increase to preserve the funds in the pool for all members.”

The LSSA said road accident victims will be uniquely discriminated against by the proposed legislation.

“Their rights to be compensated for harm suffered by the fault of another will be taken away. Persons who suffer harm from medical negligence or are injured in train or plane or boat accidents or in shopping centres, hotels, construction sites, holiday resorts, private homes or by electrocution or pollution and by a host of other causes, have unfettered rights to seek compensation from the person or entity who caused them harm.

“Innocent motor vehicle accident victims, alone, do not have this right, despite the fact that they pay premiums to the fund.”

At present, injuries sustained in a motor car accident anywhere in South Africa by any person are covered by the Fund.

The Bill now excludes injuries suffered in motor vehicle accidents in parking areas, sports fields, farm roads, driveways, private estates, game reserves or any other private road.

People who are not citizens or permanent residents are also not covered.

Persons crossing a highway are not covered. Persons injured in a hit and run are not covered. Pedestrians, drivers and cyclist who may test over the legal limit for alcohol and their dependents are not covered.

The Bill also proposes doing away with payments for pain and suffering, loss of amenities of life, disability, disfigurement or shock.

It also does away with lump sum payments for loss of earnings or support, replacing them with monthly payments, and giving the fund the right to continually reassess its liability to continue to pay.

While at present all medical and other expenses reasonably incurred that arise directly from the accident are covered, these will now be subject to a prescribed tariff. Any future medical expenses have to be pre-authorised.

The LSSA said the Bill also largely ousts the role of the courts in determining contested claims, establishing instead alternative dispute resolution procedures followed by referral to be a yet-to-be established Road Accident Fund Adjudicator.

Co-chair of the KZN Personal Injury Lawyers Association Anthony De Sousa said the biggest issues around the Bill was what was not known, such as what “social benefits” were and what the treatment tariffs would be.

“We don’t know what we are signing up for”.

“What also worries me is the people it excludes, such as pedestrians crossing highways. They don’t do that for fun. They do it because they have no choice and are trying to get to work or home.

“They are poor people and if they are knocked down, they really need help. To exclude them is just weird.”

He said while there may be a case not to cover motorists who don’t have licences, or who are over the legal alcohol limit, the Bill also proposed that their dependents are not covered, such as a child who is injured.

“The kids are not at fault, but suddenly they have no claim.”

He said the approach seemed to be: “Let’s try and save some money”.

“We pay a lot of money to the fund in terms of the levy. If you were to take that money and take up an insurance policy, you would probably get better cover and better value for money.

“I don’t think, no matter how they change it, it won’t work until they sort out the dysfunctionality, the administrative inefficiencies in the fund. You can change it to whatever system. They cannot properly administer it and run it.

“If they did their jobs properly, the fund would be saving itself a bucket load of money.”

De Sousa said the association was presently putting together its formal response to the proposals.

Collen Msibi, spokesperson for the Department of Transport said, “The bill is out for comments. The department will welcome all views and suggestions for its consideration.”

Comments and objections can be sent to Lindiwe Twala at twala@dot.gov.za or Trevor Mphahlele at mphahlelet@dot.gov.za

The deadline for comments is 8 October.

Republished from GroundUp under a Creative Commons Attribution-NoDerivatives 4.0 International License.

Source: GroundUp