Urea: A Major Cause of Dementia

Urea has been pinpointed as the cause of at least two, if not all, kinds of dementia. Amazing! A common metabolite of the body can cause dementia. Hopefully ways to prevent this will be forthcoming shortly.

https://www.technologynetworks.com/neuroscience/news/increased-urea-levels-in-brain-linked-with-dementia-295066

An international team of scientists have confirmed the discovery of a major cause of dementia, with important implications for possible treatment and diagnosis.

Professor Garth Cooper from The University of Manchester, who leads the Manchester team, says the build-up of urea in the brain to toxic levels can cause brain damage – and eventually dementia.

The work follows on from Professor Cooper’s earlier studies, which identified metabolic linkages between Huntington’s, other neurodegenerative diseases and type-2 diabetes.

The team consists of scientists from The University of Manchester, the University of Auckland, AgResearch New Zealand, the South Australian Research and Development Institute, Massachusetts General Hospital and Harvard University.

The latest paper by the scientists, published today in the Proceedings of the National Academy of Sciences, shows that Huntington’s Disease – one of seven major types of age-related dementia – is directly linked to brain urea levels and metabolic processes.

Their 2016 study revealing that urea is similarly linked to Alzheimer’s, shows, according to Professor Cooper, that the discovery could be relevant to all types of age-related dementias.

The Huntington’s study also showed that the high urea levels occurred before dementia sets in, which could help doctors to one day diagnose and even treat dementia, well in advance of its onset.

Urea and ammonia in the brain are metabolic breakdown products of protein. Urea is more commonly known as a compound which is excreted from the body in urine. If urea and ammonia build up in the body because the kidneys are unable to eliminate them, for example, serious symptoms can result.

Professor Cooper, who is based at The University of Manchester’s Division of Cardiovascular Sciences, said: “This study on Huntington’s Disease is the final piece of the jigsaw which leads us to conclude that high brain urea plays a pivotal role in dementia.

“Alzheimer’s and Huntington’s are at opposite ends of the dementia spectrum – so if this holds true for these types, then I believe it is highly likely it will hold true for all the major age-related dementias.

“More research, however, is needed to discover the source of the elevated urea in HD, particularly concerning the potential involvement of ammonia and a systemic metabolic defect.

“This could have profound implications for our fundamental understanding of the molecular basis of dementia, and its treatability, including the potential use of therapies already in use for disorders with systemic urea phenotypes.”

Dementia results in a progressive and irreversible loss of nerve cells and brain functioning, causing loss of memory and cognitive impairments affecting the ability to learn. Currently, there is no cure.

The team used human brains, donated by families for medical research, as well as transgenic sheep in Australia.

Manchester members of the team used cutting-edge gas chromatography mass spectrometry to measure brain urea levels. For levels to be toxic urea must rise 4-fold or higher than in the normal brain says Professor Cooper.

He added: “We already know Huntington’s Disease is an illness caused by a faulty gene in our DNA – but until now we didn’t understand how that causes brain damage – so we feel this is an important milestone.

“Doctors already use medicines to tackle high levels of ammonia in other parts of the body, Lactulose – a commonly used laxative, for example, traps ammonia in the gut. So it is conceivable that one day, a commonly used drug may be able to stop dementia from progressing. It might even be shown that treating this metabolic state in the brain may help in the regeneration of tissue, thus giving a tantalising hint that reversal of dementia may one day be possible.”

This article has been republished from materials provided by The University of Manchester, UK. Note: material may have been edited for length and content. For further information, please contact the cited source.

Reference:

Handley, R. R., Reid, S. J., Brauning, R., Maclean, P., Mears, E. R., Fourie, I., . . . Snell, R. G. (2017). Brain urea increase is an early Huntington’s disease pathogenic event observed in a prodromal transgenic sheep model and HD cases. Proceedings of the National Academy of Sciences, 201711243. doi:10.1073/pnas.1711243115

Study shows vagus nerve stimulation significantly reduces rheumatoid arthritis symptoms

This is amazing! Implanting a small bioelectronic device on the Vagus nerve in Rheumatoid arthritic (RA) patients makes markers of inflammation (such as TNF and other cytokines) go down. And not only that, the symptoms of RA are also decreased.

This can be used for other autoimmune and immune diseases as well.

https://www.technologynetworks.com/neuroscience/news/study-shows-vagus-nerve-stimulation-significantly-reduces-rheumatoid-arthritis-284383

Clinical trial data published in the Proceedings of the National Academy of Sciences (PNAS) demonstrates stimulating the vagus nerve with an implantable bioelectronic device significantly improved measures of disease activity in patients with rheumatoid arthritis (RA). RA is a chronic inflammatory disease that affects 1.3 million people in the United States and costs tens of billions of dollars annually to treat. The findings were announced by the Academic Medical Center/University of Amsterdam, the Feinstein Institute for Medical Research and SetPoint Medical.

See Also: Neurostimulation: What is being said in the media and academic literature?

The publication highlights a human study designed to reduce symptoms of RA, cytokine levels and inflammation by stimulating the vagus nerve with a small implanted device.

“This is the first study to evaluate whether stimulating the inflammatory reflex directly with an implanted electronic device can treat RA in humans,” said Professor Paul-Peter Tak, MD, PhD, FMedSci, the international principal investigator and lead author of the paper at the Division of Clinical Immunology & Rheumatology of the Academic Medical Center/University of Amsterdam. “We have previously shown that targeting the inflammatory reflex may reduce inflammation in animal models and in vitro models of RA. The direct correlation between vagus nerve stimulation and the suppression of several key cytokines like TNF as well as reduced RA signs and symptoms demonstrates proof of mechanism, which might be relevant for other immune-mediated inflammatory diseases as well.”

“Our findings suggest a new approach to fighting diseases with bioelectronic medicines, which use electrical pulses to treat diseases currently treated with potent and relatively expensive drugs,” said Anthony Arnold, Chief Executive Officer of SetPoint Medical. “These results support our ongoing development of bioelectronic medicines designed to improve the lives of people suffering from chronic inflammatory diseases and give healthcare providers new and potentially safer treatment alternatives at a much lower total cost for the healthcare system.”

“This is a real breakthrough in our ability to help people suffering from inflammatory diseases,” said co-author Kevin J. Tracey, MD, president and CEO of the Feinstein Institute for Medical Research, discoverer of the inflammatory reflex and co-founder of SetPoint Medical. “While we’ve previously studied animal models of inflammation, until now we had no proof that electrical stimulation of the vagus nerve can indeed inhibit cytokine production and reduce disease severity in humans. I believe this study will change the way we see modern medicine, helping us understand that our nerves can, with a little help, make the drugs that we need to help our body heal itself.”

Learn More: New non-invasive form of vagus nerve stimulation works to treat depression

While focused on rheumatoid arthritis, the trial’s results may have implications for patients suffering from other inflammatory diseases, including Crohn’s, Parkinson’s, Alzheimer’s and others.

Study methodology and results

In the study, a stimulation device was implanted on the vagus nerve during a surgical procedure, then activated and deactivated based on a set schedule to measure response over 84 days, with primary endpoints measured at day 42 using DAS28-CRP, a standard disease activity composite score for RA that includes counts of tender and swollen joints, patient’s and physician’s assessment of disease activity and serum C-reactive protein (CRP) levels.

Of 17 patients with active RA in the study, several patients that had failed to respond to multiple therapies, including biologicals with different mechanisms of action, demonstrated robust responses. The findings indicate that active electrical stimulation of the vagus nerve inhibits TNF production in RA patients and significantly attenuates RA disease severity.

Don’t Miss: The neurons in our gut help the immune system keep inflammation in check

Several patients reported significant improvements, including some who had previously failed to respond to any other form of pharmaceutical treatment. In addition, no serious adverse side effects were reported.

The emerging field of bioelectronic medicine aims to target disorders traditionally treated with drugs and instead uses advanced neuromodulation devices that may offer significant advantages. SetPoint is developing a novel proprietary bioelectronic medicine platform to treat a variety of immune-mediated inflammatory diseases, using an implanted device to stimulate the vagus nerve.

Note: Material may have been edited for length and content. For further information, please contact the cited source.

Rare form of dwarfism confers protection against bipolar affective disorder.

This is pretty amazing! Just wanted to reblog it. Would I rather rather have this form of dwarfism so I could be protected from having bipolar disorder? I do believe I would!

Bipolar1Blog

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In doing studies with Amish people for over 40 years in Pennsylvania, and then analyzing the data, the authors of this paper noticed that a rare form of dwarfism caused by a homozygous recessive mutation in a gene called Sonic Hedgehog (named by nerds who work on drosophila genetics, as they discovered this gene) is NEVER comorbid with bipolar disorder. Sonic Hedgehog is a gene involved in embryogenesis! So a mutation in it can affect many pathways downstream. But since people who have this form of dwarfism NEVER have bipolar d/o, it is thought that Sonic Hedgehog may be protective against bipolar d/o. Now to find out what does the Sonic Hedgehog gene do that is protective. Might take a while… But a very interesting article. And hopefully helpful to us sooner than later.

http://www.nature.com/mp/journal/vaop/ncurrent/abs/mp2014118a.html

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Sexual harassment, all over the press, hits close to home

Yesterday was literally the first day after months, I said to myself that I’m finally feeling better. The heaviness, the panic about my son, the anxiety, all seemed to have abated!

Then I went to see an endocrinologist whom I hadn’t seen in a couple of years. He sort of grilled me about why I hadn’t come to see him. I said my psychiatrist had recommended someone else. Anyway, we got through that or so i thought.

Then he put his stethoscope in his ears, came at me and roughly pulled my button down shirt out, stuck his nose sort of inside my shirt, to get a good look I assume, then stuck the stethoscope inside my shirt to listen to my heart!!

Then he walked behind me, yanked my shirt out of my pants, had a good look at my butt and stuck The stethoscope inside my shirt on my back to listen to my lungs!!

Now why did he have to do that? He did not have to yank and tug at my shirt. He could have listened to my heart and lungs perfectly well from the outside of my shirt.

It all happened so quickly, I had no time to protest or react. I’m kicking myself that I didn’t tell him to stop.

Obviously, I’m not going back to him and I am writing him a letter on which I will cc the AMA and send a copy to the complaints department of the AMA.

Whether he is angry or a voyeur or both, he definitely should have some consequences for his sick actions.

Very disappointed and feel pretty bad again. Damn him for taking my hard won peace of mind.

I don’t look sick.

Why is it that when we are physically ill, as in for example having the flu, we are allowed to rest and recuperate. However when the illness is mental, as for example a mixed episode of bipolar disorder, we are not allowed to rest. We must keep going as if we are not sick at all. If we are housewives, dinner must be on the table when the family gets home. If we don’t make dinner (just an example of work) then why didn’t we? People might say “You don’t look sick, why don’t you do your work?” I have been in a mixed phase, as I generally am in the Fall. I feel terrible, emotional, terribly anxious, weepy, nothing good. Can’t eat. Yet I’m not given much of a chance to rest. I don’t look sick.