Tag: 2/5/24

Categories : Cardiovascular Disease GeneticsTags :

Rare Longevity Mutation may Also Reduce Cardiovascular Disease Risk

On By ModernMedia
Photo by Sangharsh Lohakare on Unsplash

People with a rare longevity condition known as growth hormone receptor deficiency (GHRD) may also have possible cardiovascular health advantages. Also called Laron syndrome, GHRD, which is characterised by the body’s impaired ability to use its own growth hormone and results in stunted growth, has been linked in mice to a record 40% longevity extension and lower risks for various age-related diseases.

The risk of cardiovascular disease in individuals with GHRD has remained unclear until now, leading to the speculation that in people, this mouse longevity mutation may actually increase cardiovascular disease. In humans, unlike mice, GHRD is not associated with an extended lifespan.

The study, appearing in Med, is the latest product of an international collaboration spanning nearly 20 years between Valter Longo, professor of gerontology at the USC Leonard Davis School of Gerontology, and endocrinologist Jaime Guevara-Aguirre of the Universidad San Francisco de Quito, Ecuador.

Over the past two decades, Longo, Guevara-Aguirre and colleagues have examined the health and aging of people with the gene mutation that causes GHRD. This rare mutation, found in just 400 to 500 people worldwide, was identified in a group of Ecuadorians whose ancestors had fled Spain during the Inquisition more than three centuries ago. The mutation leaves them with ineffective growth hormone receptors and results in a type of dwarfism.

The team’s previous research has indicated that while GHRD/Laron syndrome reduces growth, it also appears to reduce the risk of several age-related diseases. Although the Ecuadorians with GHRD have a higher rate of obesity, they have a very low risk of cancer and Type 2 diabetes. They also appear to have healthier brains and better performance on tests of cognition and memory.

For the current study, the research team examined cardiovascular function, damage, and risk factors in GHRD subjects and their relatives. Researchers conducted two phases of measurements in Los Angeles and Ecuador, involving a total of 51 individuals, with 24 diagnosed with GHRD and 27 relatives without GHRD serving as controls.

Key findings from the study included:

  • GHRD subjects displayed lower blood sugar, insulin resistance, and blood pressure compared to the control group.
  • They also had smaller heart dimensions and similar pulse wave velocity (a measure of stiffness in the arteries) but had lower carotid artery thickness compared to control subjects.
  • Despite elevated low-density lipoprotein (LDL) levels, GHRD subjects showed a trend for lower carotid artery atherosclerotic plaques compared to controls (7% vs 36%).

“These findings suggest that individuals with GHRD have normal or improved levels of cardiovascular disease risk factors compared to their relatives,” said Longo, senior author of the new study. “Although the population tested is small, together with studies in mice and other organisms this human data provide valuable insights into the health effects of growth hormone receptor deficiency and suggest that drugs or dietary interventions that cause similar effects could reduce disease incidence and possibly extend longevity.”

Source: University of Southern California

Categories : Injury & Trauma Metabolic DisordersTags :

Neurons Cause Metabolic Havoc after Spinal Injury

On By ModernMedia

Conditions such as diabetes, heart attack and vascular diseases commonly diagnosed in people with spinal cord injuries can be traced to abnormal post-injury neuronal activity that causes abdominal fat tissue compounds to leak and pool in the liver and other organs, a new animal study published in Cell Reports Medicine has found.

After discovering the connection between dysregulated neuron function and the breakdown of triglycerides in fat tissue in mice, researchers found that a short course of the drug gabapentin, commonly prescribed for nerve pain, prevented the damaging metabolic effects of the spinal cord injury – though not without side effects.

Gabapentin inhibits a neural protein that, after the nervous system is damaged, becomes overactive and causes communication problems – in this case, affecting sensory neurons and the abdominal fat tissue to which they’re sending signals.

“We believe there is maladaptive reorganisation of the sensory system that causes the fat to undergo changes, initiating a chain of reactions – triglycerides start breaking down into glycerol and free fatty acids that are released in circulation and taken up by the liver, the heart, the muscles, and accumulating, setting up conditions for insulin resistance,” said senior author Andrea Tedeschi, assistant professor of neuroscience in The Ohio State University College of Medicine.

“Through administration of gabapentin, we were able to normalise metabolic function.”

Previous research has found that cardiometabolic diseases are among the leading causes of death in people who have experienced a spinal cord injury. These often chronic disorders can be related to dysfunction in visceral white fat (or adipose tissue), which has a complex metabolic role of storing energy and releasing fatty acids as needed for fuel, but also helping keep blood sugar levels at an even keel.

Earlier investigations of these diseases in people with neuronal damage have focused on adipose tissue function and the role of the sympathetic nervous system, but also a regulator of adipose tissue that surrounds the abdominal organs.

Instead, Debasish Roy, a postdoctoral researcher in the Tedeschi lab and first author on the paper, decided to focus on sensory neurons in this context. Tedeschi and colleagues have previously shown that a neuronal receptor protein called alpha2delta1 is overexpressed after spinal cord injury, and its increased activation interferes with post-injury function of axons, the long, slender extensions of nerve cell bodies that transmit messages.

In this new work, researchers first observed how sensory neurons connect to adipose tissue under healthy conditions, and created a spinal cord injury mouse model that affected only those neurons – without interrupting the sympathetic nervous system.

Experiments revealed a cascade of abnormal activity within seven days after the injury in neurons – though only in their communication function, not their regrowth or structure – and in visceral fat tissue. Expression of the alpha2delta1 receptor in sensory neurons increased as they over-secreted a neuropeptide called CGRP, all while communicating through synaptic transmission to the fat tissue – which, in a state of dysregulation, drove up levels of a receptor protein that engaged with the CGRP.

“These are quite rapid changes. As soon as we disrupt sensory processing as a result of spinal cord injury, we see changes in the fat,” Tedeschi said. “A vicious cycle is established – it’s almost like you’re pressing the gas pedal so your car can run out of gas but someone else continues to refill the tank, so it never runs out.”

The result is the spillover of free fatty acids and glycerol from fat tissue, a process called lipolysis, that has gone out of control. Results also showed an increase in blood flow in fat tissue and recruitment of immune cells to the environment.

“The fat is responding to the presence of CGRP, and it’s activating lipolysis,” Tedeschi said. “CGRP is also a potent vasodilator, and we saw increased vascularisation of the fat – new blood vessels forming as a result of the spinal cord injury. And the recruitment of monocytes can help set up a chronic pro-inflammatory state.”

Silencing the genes that encode the alpha2delta1 receptor restored the fat tissue to normal function, indicating that gabapentin – which targets alpha2delta1 and its partner, alpha2delta2 – was a good treatment candidate. Tedeschi’s lab has previously shown in animal studies that gabapentin helped restore limb function after spinal cord injury and boosted functional recovery after stroke.

But in these experiments, Roy discovered something tricky about gabapentin: the drug prevented changes in abdominal fat tissue and lowered CGRP in the blood, in turn preventing spillover of fatty acids into the liver a month later, establishing normal metabolic conditions. But paradoxically, the mice developed insulin resistance, a known side effect of gabapentin.

The team instead tried starting with a high dose, tapering off and stopping after four weeks.

“This way, we were able to normalise metabolism to a condition much more similar to control mice,” Roy said. “This suggests that as we discontinue administration of the drug, we retain beneficial action and prevent spillover of lipids in the liver. That was really exciting.”

Finally, researchers examined how genes known to regulate white fat tissue were affected by targeting alpha2delta1 genetically or with gabapentin, and found both of these interventions after spinal cord injury suppress genes responsible for disrupting metabolic functions.

Tedeschi said the combined findings suggest starting gabapentin treatment early after a spinal cord injury may protect against detrimental conditions involving fat tissue that lead to cardiometabolic disease – and could enable discontinuing the drug while retaining its benefits and lowering the risk for side effects.

Source: Ohio State University

Categories : NeurologyTags :

The First Half of a Night’s Sleep Resets Brain Connections

On By ModernMedia

…but not the second half

Source: CC0

During a night’s sleep, the brain weakens the new connections between neurons that had been forged while awake – but only during the first half, according to a new study in fish by UCL scientists.

The researchers say that their findings, published in Nature, provide insight into the role of sleep, but still leave an open question around what function the latter half of a night’s sleep serves.

The researchers say the study supports the Synaptic Homeostasis Hypothesis, a key theory on the purpose of sleep which proposes that sleeping acts as a reset for the brain.

Lead author Professor Jason Rihel (UCL Cell & Developmental Biology) said: “When we are awake, the connections between brain cells get stronger and more complex. If this activity were to continue unabated, it would be energetically unsustainable. Too many active connections between brain cells could prevent new connections from being made the following day.

“While the function of sleep remains mysterious, it may be serving as an ‘off-line’ period when those connections can be weakened across the brain, in preparation for us to learn new things the following day.”

For the study, the scientists used optically translucent zebrafish, with genes enabling synapses to be easily imaged. The research team monitored the fish over several sleep-wake cycles.

The researchers found that brain cells gain more connections during waking hours, and then lose them during sleep. They found that this was dependent on how much sleep pressure (need for sleep) the animal had built up before being allowed to rest; if the scientists deprived the fish from sleeping for a few extra hours, the connections continued to increase until the animal was able to sleep.

Professor Rihel added: “If the patterns we observed hold true in humans, our findings suggest that this remodelling of synapses might be less effective during a mid-day nap, when sleep pressure is still low, rather than at night, when we really need the sleep.”

The researchers also found that these rearrangements of connections between neurons mostly happened in the first half of the animal’s nightly sleep. This mirrors the pattern of slow-wave activity, which is part of the sleep cycle that is strongest at the beginning of the night.

First author Dr Anya Suppermpool (UCL Cell & Developmental Biology and UCL Ear Institute) said: “Our findings add weight to the theory that sleep serves to dampen connections within the brain, preparing for more learning and new connections again the next day. But our study doesn’t tell us anything about what happens in the second half of the night. There are other theories around sleep being a time for clearance of waste in the brain, or repair for damaged cells – perhaps other functions kick in for the second half of the night.”

Source: University College London

Categories : Injury & Trauma Obstetrics & GynaecologyTags :

Menstrual Cycle Phases Linked to Increased Injury Risk for Female Athletes

On By ModernMedia
Photo by Ashley Williams

Football players in England’s top-tier WSL were six times more likely to experience a muscle injury in the days leading up to their period compared to when they were on their period, according to a new study published in Medicine & Science in Sports & Exercise.

This the first prospective longitudinal study monitoring menstrual cycles alongside injuries in female footballers. The findings suggest there could be increased injury risk windows at particular times in the cycle.

Despite being a relatively small sample size, the data demonstrates the need to consider the menstrual cycle in elite sports, to reduce injury risk and to support the wellbeing of athletes.

Menstrual cycle symptoms are common and around two thirds of elite athletes feel that these can have negative impacts on their performance. There has been little previous research tracking injuries alongside the menstrual cycle in female sport, despite much speculation and anecdotal evidence suggesting that there may be some key times for increased injury risk. Given the increased professionalism, interest, growth, and investment in women’s sport, the authors say further research in this area is needed.

In this study, researchers at UCL and the University of Bath recorded time-loss injuries and menstrual cycle data for elite female football players across three seasons. All of the players were based at one Women’s Super League (WSL) club, the top tier of women’s football in England. During the study they tracked 593 cycles across 13 390 days, in which time 26 players experienced 74 injuries.

The authors divided each cycle into four main phases in their study. Each phase comes with assumed hormonal changes that have the potential to influence different aspects of a woman’s health and wellbeing.

Ally Barlow, first author of the study from the University of Bath and a physiotherapist at the WSL club, said: “We have been tracking player’s menstrual cycles for a number of seasons to observe trends in terms of symptoms and cycle characteristics. We were interested to learn more about the potential association between injury risk across the menstrual cycle. This study set out to collect specific scientific data so that we could learn more about the menstrual cycle and player’s injury risk.”

Analysis of the data found that players were six times more likely in the pre-menstrual phase (oestrogen and progesterone decrease to bring about the onset of menstruation) and five times more likely in the early-mid luteal phase (after ovulation when both oestrogen and progesterone are assumed to increase and remain high) to experience a muscle injury, compared to when they were in the menstrual phase.

Dr Georgie Bruinvels, senior author of the study from UCL Surgery & Interventional Science and the Institute of Sport, Exercise & Health (ISEH), said: “While these results must be viewed with caution, this data highlights a need to investigate this area further. Given the growth of women’s sport it’s an exciting time to be working in female physiology, but there are a number of known challenges when conducting research with female athletes, in part explaining why there is such a significant sex data gap.

“Conducting large-scale research is complex but must be prioritised to best support female athletes, and we hope studies like this will pave the way for this. Every woman has their own unique physiology, so it’s crucial to support and empower them in the right ways. If future research demonstrates that there are risk windows for certain injury types, we should be proactive in mitigating these risks to enable female athletes to exercise and compete on any given day.”

The authors emphasise that further data collected in a standardised manner is needed before the sports science community can start to look for biological explanations for this increased injury risk.

Dr Jo Blodgett, an author of the study from UCL Surgery & Interventional Science and the Institute of Sport, Exercise & Health (ISEH), said: “Though our sample size for this research was relatively small, we observed clear links between cycle phase and injury prevalence, and the size of the association – six times higher in the premenstrual phase and five times higher in the early-mid luteal phase for muscular injuries – was quite large.

“To better understand the variability in injury risk across the cycle we need more players and teams to continually track injury incidence, menstrual cycle and symptoms in a standardised manner. At the elite level, injuries to your squad can mean the difference between winning and losing, the difference between being crowned champions and runners-up. But perhaps more importantly, it means pain and suffering for players that could perhaps be avoided with better player-centred support.”

Source: University College London

Categories : CancerTags :

Activists and Patients March on Gauteng Health Department Demanding Radiation Treatment

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Nearly R800-million set aside for radiation treatment outsourcing has not been spent

Activists and patients marched on Tuesday in Johannesburg demanding radiation treatment for cancer. Photo: Silver Sibiya

By Silver Sibiya for GroundUp

Activists and cancer patients marched to the offices of the Gauteng department of health on Tuesday demanding that millions of rands allocated for radiation treatment for cancer patients be used.

SECTION27, Cancer Alliance and Treatment Action Campaign (TAC) called for the department to use R784-million set aside by the provincial treasury in March 2023 to outsource radiation treatment. They say not a single patient has received treatment through this intervention a year later.

In an open letter to health MEC Nomantu Nkomo-Ralehoko last week, Khanyisa Mapipa from SECTION27, Salomé Meyer from the Cancer Alliance and Ngqabutho Mpofu from TAC said that in March 2022, Cancer Alliance had compiled a detailed list of approximately 3000 patients who were awaiting radiation oncology treatment.

They said there were shortages of staff in the two radiation oncology centres in Gauteng, Steve Biko Academic Hospital and Charlotte Maxeke Johannesburg Academic Hospital. Charlotte Maxeke Hospital had only two operational machines compared to seven in 2020. Tenders for new equipment had been delayed and the backlog of patients was increasing, they said.

As a result, SECTION27 and Cancer Alliance had asked the provincial treasury to set aside R784-million to outsource radiation treatment. The money had been allocated in March 2023, but a year later, no service provider had been appointed.

“It has actually been four years since the matter was brought to the Department of Health,” said Mapipa on Tuesday. She said cancer patients were not getting the treatment they needed.

“We as Cancer Alliance and SECTION27 ran to Gauteng Treasury to ask them to allocate these funds. Gauteng Treasury responded and they gave this money, but this money is still sitting.”

Thato Moncho, who was diagnosed with breast cancer in September 2020, is one of the patients on the waiting list. She said she had faced many delays in her treatment. “I’ve had three recurrences of cancer and I need to have radiation six weeks after my surgery, which they failed to give me. I have pleaded with the MEC of Health and the Chief Executive Officer at Charlotte Maxeke to speed up the process so I can get my radiation but they failed.”

“I’m pleading: help us so we can get radiation to live a normal life with our family.”

Gauteng Department of Health spokesperson Motalatale Modiba said the department had received the memorandum and would respond to it. He acknowledged that there had been delays which he said were caused by tender processes.

“It is in our interest to ensure that we get to address the backlog of those that require treatment, and the department will formally respond to the concerns that have been raised.” He said a tender had been awarded.

“In May the process to treat patients will start in both hospitals.”

“The respective heads of oncology in Charlotte Maxeke and Steve Biko hospitals are busy with that process of onboarding.”

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

Source: GroundUp