Tag: 23/6/23

Categories : Injury & Trauma Pain ManagementTags :

Antihypertensive Drug Prazosin could Relieve Posttraumatic Headaches

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Researchers have shown that the antihypertensive drug prazosin can prevent posttraumatic headaches, such as those caused by a concussion suffered by members of the military. Their findings were published in Headache: The Journal of Head and Face Pain.

Senior study author Dr Murray Raskind explained that few treatment options exist for this type of headache: “Persistent posttraumatic headaches are the most common long-term consequence of mild traumatic brain injuries (concussions) in Veterans and active-duty service members, causing substantial distress and disability at home and work. Although these headaches usually resemble migraine headaches symptomatically, they often fail to respond to the prevention treatments useful for migraines.”

The FDA approved prazosin to treat hypertension in 1976. It has been widely used off-label to treat conditions such as PTSD-associated nightmares and enlarged prostate. An earlier study by members of the research group suggested that prazosin could reduce the frequency and severity of headaches caused by traumatic brain injury (TBI).

To test this effect, researchers led by VA Puget Sound Health Care System conducted a pilot study with 48 Veterans and service members with headaches caused by mild TBI, also known as a concussion. Participants took gradually increasing doses of prazosin for five weeks before receiving the maximum dose for 12 weeks. The study showed that the drug was well-tolerated, and researchers reported that morning drowsiness was the only adverse effect.

Before the trial began, study participants had an average of 18 headache days each month. By the end of the 12-week period, those taking prazosin only had headaches for an average of six days a month. Participants receiving a placebo reported some reduction in headaches, but still had headaches about 12 days a month. Significantly more participants in the prazosin group had at least 50% fewer headaches during the 12 weeks of taking a full dose of medication.

Participants taking prazosin also saw significant decreases in how much headaches impacted their quality of life. By the end of the trial, those taking prazosin reported that headaches had “some impact” on their daily ability to function, while participants given a placebo continued to report “severe impact” of headaches.

Larger clinical trials are needed to confirm the extent of these promising results, according to the researchers, but these initial findings offer a potential relief for a common ailment faced by many Veterans.

“This study is the only clinical trial of an oral medication to demonstrate efficacy for posttraumatic headache. Because prazosin is widely used across VA and the Department of Defense to treat PTSD trauma nightmares and sleep disruption, many VA and DOD prescribers are familiar with prescribing this generically available, inexpensive medication,” said Raskind. “Prazosin now offers an evidence-based approach to alleviate the suffering of Veterans and service members who have struggled for years with frequent posttraumatic headaches.”

Source: Veterans Affair Research Communications

Categories : NeurologyTags :

Optical Illusions Originate in the Retina, not the Brain

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The bar in the middle is all one grey level, but it appears lighter on the left and darker on the right due to the background. Credit Jolyon Troscianko

Numerous visual illusions are caused by limits in the way our eyes and visual neurones work – rather than more complex psychological processes, as demonstrated by new research published in PLOS Computational Biology.

Researchers examined illusions in which an object’s surroundings affect the way we see its colour or pattern. Scientists and philosophers have long debated whether these illusions are caused by neural processing in the eye and low-level visual centres in the brain, or involve higher-level mental processes such as context and prior knowledge.

In the new study Dr Jolyon Troscianko, from the University of Exeter, co-developed a model that suggests simple limits to neural responses – not deeper psychological processes – explain these illusions.

“Our eyes send messages to the brain by making neurones fire faster or slower,” said Dr Troscianko. “However, there’s a limit to how quickly they can fire, and previous research hasn’t considered how the limit might affect the ways we see colour.”

The model combines this “limited bandwidth” with information on how humans perceive patterns at different scales, together with an assumption that our vision performs best when we are looking at natural scenes.

The model was developed by researchers from the Universities of Exeter and Sussex to predict how animals see colour, but it was also found to correctly predict many visual illusions seen by humans.

“This throws into the air a lot of long-held assumptions about how visual illusions work,” Dr Troscianko said.

He said the findings also shed light on the popularity of high-definition televisions.

“Modern high dynamic range televisions create bright white regions that are over 10 000 times brighter than their darkest black, approaching the contrast levels of natural scenes,” Dr Troscianko added.

“How our eyes and brains can handle this contrast is a puzzle because tests show that the highest contrasts we humans can see at a single spatial scale is around 200:1.

“Even more confusingly, the neurones connecting our eyes to our brains can only handle contrasts of about 10:1.

“Our model shows how neurones with such limited contrast bandwidth can combine their signals to allow us to see these enormous contrasts, but the information is ‘compressed’ – resulting in visual illusions.

“The model shows how our neurones are precisely evolved to use of every bit of capacity.

“For example, some neurones are sensitive to very tiny differences in grey levels at medium-sized scales, but are easily overwhelmed by high contrasts.

“Meanwhile, neurones coding for contrasts at larger or smaller scales are much less sensitive, but can work over a much wider range of contrasts, giving deep black-and-white differences.

“Ultimately this shows how a system with a severely limited neural bandwidth and sensitivity can perceive contrasts larger than 10 000:1.”

Source: University of Exeter

Categories : Antibiotics Obstetrics & GynaecologyTags :

Targeting A Particular Bacteria Reduced Endometriosis Lesions

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Photo by Andrea Piacquadio on Pexels

A research group from Nagoya University in Japan has discovered that using an antibiotic to target Fusobacterium reduced the formation of lesions associated with endometriosis, a gynaecological disorder characterised by endometrial tissue growing outside of the uterus. Their findings, published in Science Translational Medicine, suggest an alternative treatment for this disorder based on antibiotics.

Endometriosis affects one in ten women between the ages of 15 and 49. The disorder can cause lifelong health problems, including pelvic pain and infertility. Although it can be treated using hormone therapy and surgical resection, these procedures sometimes lead to side effects, recurrence, and a significant impact on pregnancy.

The group led by Professor Yutaka Kondo (he, him) and Assistant Professor Ayako Muraoka (she, her) from the Nagoya University Graduate School of Medicine, in collaboration with the National Cancer Center, found that the uterus of mice infected with Fusobacterium had more and heavier lesions. However, mice that had been given an antibiotic to eradicate Fusobacterium saw improved lesion formation.

The team’s findings strongly suggest that targeting Fusobacterium is an effective non-hormonal antibiotic treatment for endometriosis. Dr Kondo praised the potential for easier diagnosis and treatment. “Eradication of this bacterium by antibiotic treatment could be an approach to treat endometriosis for women who are positive for fusobacteria infection, and such women could be easily identified by vaginal swab or uterus swab,” he said.

This study also shows the benefit of looking at upstream events to determine causative agents. The initial finding was that a protein called transgelin (TAGLN) was often upregulated in patients with endometriosis. This was unsurprising because the protein is associated with processes that are important in the development of endometriosis. However, this finding led them to determine that transforming growth factor beta (TGF-β) seemed to cause the upregulation of TAGLN. Since TGF-β is released by macrophages, the natural anti-inflammatory response and immune regulation cells of the body, this led them to conclude that these macrophages were being activated in response to Fusobacterium.

“In this study, we demonstrated that the Fusobacterium-TAGLN-endometriosis axis is frequently dysregulated in endometriosis,” said Dr Kondo. “Our data provide a strong and novel rationale for targeting Fusobacterium as a non-hormonal antibiotic-based treatment for endometriosis.”

Clinical trials of antibiotic treatment for human patients are ongoing at the Department of Obstetrics and Gynecology at Nagoya University Hospital.

Source: Nagoya University

Categories : Ageing Obstetrics & GynaecologyTags :

Rethink Needed for the Genetic Cause of Very Early Menopause

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A new study showed that it may be necessary to rethink the genetic cause previously held to be behind very early menopause. Until now, variants in any one of more than 100 genes were thought to cause premature ovarian insufficiency (POI), which results in menopause before age 40. This affects around 1% of women, making it a leading cause of infertility. Under current guidance, a variation in one of these genes is cause for clinicians to consider a genetic diagnosis of POI.

Now, in the largest study to date, published in Nature Medicine, researchers analysed genetic data from more than 104 733 women in UK Biobank, of whom 2231 reported experiencing menopause before the age of 40.

The study found evidence that 98% of women carrying variations in the genes that were previously considered to be causes of premature menopause in fact had menopause over 40, therefore ruling out a diagnosis of POI in these women.

Anna Murray, Professor of Human Genetics at the University of Exeter Medical School is a senior author on the study. She said: “Our research means rethinking what causes very early menopause. The presence of specific genetic variants in multiple women who experience premature menopause has led to the assumption that they are causing the condition – but we have shown that these gene variations are also found in women with a normal age of menopause and therefore in many cases the link could just be coincidence. It now seems likely that premature menopause is caused by a combination of variants in many genes, as well as non-genetic factors. As genomic medicine evolves, we need to apply this standard of evidence to other conditions, so we can tailor diagnosis, treatment and support.”

Dr Julia Prague, Consultant Endocrinologist and Clinical Academic at the University of Exeter, and an author on the paper, said: “Having a very early menopause is often extremely distressing because it means losing fertility and treatment with hormone replacement is required to prevent negative health consequences. Clinicians need to understand the reasons why premature menopause occurs so that they do not miss the true underlying cause and can counsel patients appropriately. Misinterpreting genetic tests could have negative implications for women, such as suggesting that their relatives may also be at risk of very early menopause due to their genes, when in fact they may not be.”

Stasa Stankovic, of the University of Cambridge’s MRC Epidemiology Unit, and co-lead analyst of the study, said: “Each woman’s unique genetic combination shifts menopause timing, either earlier or later. Although genetic variation in the studied genes were not sufficient to cause very early menopause, we did identify genetic drivers that had a much more subtle impact on reproductive longevity. For example, women carrying genetic variation in TWNK and SOHLH2 genes experienced menopause up to three years earlier than the general population. Our future studies will continue using the power of human genomics to better understand the underlying biology of reproductive ageing in women and key genetic drivers of its extreme forms, including very early menopause. With this knowledge, we are also paving the path towards development of next-generation treatments for reproductive disorders.”

Source: University of Exeter

Categories : Cardiovascular Disease Diseases, Syndromes and ConditionsTags :

Even Modest Drop in Kidney Function is Linked to Greater Health Risks

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A Canadian study of more than 8 million adults suggests that even a modest loss of kidney function is associated with increased health risks. The study, published in The BMJ, could lead to better approaches to prevent chronic kidney disease and related conditions, particularly in younger adults.

“The dogma is that healthy, young adults don’t need to worry about kidney function unless it drops to around 50% of the normal level, but our research suggests that even a more modest 20–30% drop may have consequences and we may want to have earlier conversations about prevention and monitoring,” explained senior author Dr Manish Sood at the University of Ottawa.

The research team used health records from 2008 to 2021 for every Ontario, Canada adult aged 18–65 who had at least one blood test for kidney function, but no history of kidney disease. They found that 18% of those in the 18–39 age group had kidney function that was modestly below normal levels, but not low enough to be diagnosed with chronic kidney disease. Individuals in this ‘grey zone’ faced a modestly increased risk of kidney failure, death and cardiovascular events.

For example, in young adults (age 18–39), a 20–30% loss in kidney function was associated with a 1.4-fold increase in death, 1.3-fold increase in a cardiac event and a 6-fold increase in the risk of kidney failure. The absolute risk of any of these events was still low at less than 2 per 1000.

“Thankfully, the absolute risk for any one individual with kidney function in this grey zone is low, but when we look at the whole population, the impact could be quite significant,” said co-senior author Dr Greg Knoll, senior scientist, nephrologist and Head of the Department of Medicine at The Ottawa Hospital and the University of Ottawa. “We need further research to confirm these findings and then see if we can reduce the risk through lifestyle modification.”

While the blood creatine test for kidney function is relatively inexpensive and readily available, the researchers are not suggesting routine testing for all individuals at this time. However, if an individual has had a kidney test that shows a modest reduction in function, it could prompt consulting health care provider. All individuals can also reduce their risk of kidney disease by eating a healthy diet with lower salt, exercising regularly and limiting alcohol intake.

Dr. Sood and his colleagues previously developed the Project BigLife Chronic Kidney Disease calculator to help individuals calculate their kidney disease risk and see the impact of lifestyle changes. The calculator will continue to be refined as new research arises.  

Source: EurekAlert!