Erythrocyte Deformability As a Potential Biomarker for Chronic Fatigue Syndrome, Davis et al (2018)

The dual roles of red blood cells in tissue oxygen delivery: oxygen carriers and regulators of local blood flow
Jensen, 2009

This is an interesting paper. Among other things:

Mammalian RBCs release ATP when exposed to reduced oxygen tensions, and the amount released is linked to the decrease in Hb O2 saturation (Ellsworth et al., 1995; Jagger et al., 2001). The extracellular ATP diffuses to the endothelium, where it binds to P2y purinergic receptors, which activates the synthesis of vasodilators (including nitric oxide) that relax vascular smooth muscles and increase local blood flow and O2 delivery (Ellsworth et al., 1995; Sprague et al., 2007). The local extracellular concentration of ATP in hypoxic tissue regions is in the 10–6 mol l–1 range, and ATP is clearly capable of inducing vasodilation at such concentrations (Ellsworth, 2000).
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ATP release is activated not only by PO2 decrease but also by mechanical deformation (Sprague et al., 2001), as would occur when RBCs are squeezed through narrow vessels.
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So red blood cells release ATP when they sense hypoxic tissues (this occurs during exercise when muscles require more oxygen) but also apparently when they are mechanically deformed (squeezed). That released ATP activates the synthesis of vasodilators including nitric oxide which then increase the size of blood vessels so more blood can flow.
 
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Les Simpson recommended a few pharmaceuticals back in the 90's, he thought they might have some potential., Trental, Cinnarizine, Hydergine and Cyclandelate. Has anyone taken these?

The ME doctor I saw back in 1992 recommended EPO, he met LS at a seminar when he visited our city
 
Jonathan Edwards said:
I don't think contact actually matters for oxygen exchange. Molecules the size of oxygen zip through tissue as if there was nothing in the way. And contact does not make anything any thinner. The capillary still has the same diameter and the cell is in the middle of it.
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The only thing I think might matter with contact is regulatory molecules, such as eicosanoids. However at this point I do not see good evidence that this matters.

Oxygen release is probably more important, and that is regulated by a number of factors. Indeed if the acidity rises in a region then more oxygen will be dumped. That is likely to happen in ME due to lactate, but only if the lactic acid overwhelms the buffer in that region. This does not however mean the electron transport chain will necessarily increase energy production. The problem, for now, is more likely to be elsewhere.

The fact remains that Systrom found that our venous return blood is too highly oxygenated. Its not being dumped or its not being used.
 
Sunshine3 said:
Why would evening primrose oil cause problems?
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This goes to issues with all eicosanoids. PGE1 is a good outcome from evening primrose oil. However many series 2 eicosanoids can also be made, including PGE2, and many of these are not good. This pathway is mostly pro-inflammatory, though also essential to life. Too much is bad and can be fatal. Many of the factors involved in ME are likely to increase PGE2 synthesis, plus other eicosanoids on that path. How its regulated is the key, and I don't think we know enough yet.

It appears that increased evening primrose oil intake may drive this path much more in ME than in many other conditions or healthy controls. This is primarily due to things that act as agonists for cyclooxygenase function, and things that might release more arachidonic acid from the cell membrane. This includes nitric oxide.

Now I am a fan of PGE1 for many conditions, as it increases blood flow. Evening primrose oil is too non-specific though. A little might help, and a little when experiencing symptoms you know benefit from it might help. A bit more is likely to be more problematic, and our needs are likely to vary. Over time this response can vary too.

So far as I am aware this kind of supplementation leads to a non-linear response. That is its not straightforward. So it cannot be relied on, but then again sometimes it might help too.

When I went into a decline in the mid 90's I benefited a lot from no longer taking evening primrose oil. Sometimes however I might benefit from taking it, and the primary warning sign for me is peeling skin. Nowadays I eat Brazil nuts instead, and get some selenium along with my omega-6 fats. This also improves my sleep.

PS Eicosanoids are a large family of hormones that are often overlooked by doctors. Its a deep and complex area, and I fully admit I do not understand them, despite investigating for years. The main reasons are the field is constantly changing, and there are so many of them, and at one point a new one was being discovered every year.
 
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Merged thread

Could Poor Microcirculation Be Causing Chronic Fatigue Syndrome (ME/CFS)?

https://www.prohealth.com/me-cfs/li...on-causing-chronic-fatigue-syndrome-cfs-88729

The idea that the blood delivery system is causing the problems with energy production is not new

By Cort Johnson • ProHealth.com • December 17, 2018

The Gist

Shungu’s brain findings suggest high levels of oxidative stress and low levels of antioxidants are constricting the blood vessels.

The blood vessel constriction is producing a low oxygen environment which forces the cells in the brain to rely on anaerobic energy production.

High levels of oxidative stress are amongst the most consistent findings in chronic fatigue syndrome (ME/CFS).

Our red blood cells provide the oxygen our cells need to do their work. In order to flow properly through the capillaries to our cells they must be round and elastic.

The SJSU/Stanford study overseeen by Ron Davis suggests that ME/CFS patient’s red blood cells are often no longer round and take longer than usual to enter the capillaries and flow through them. Their membranes are stiffer than usual as well and they contain high levels of free radicals.

The red blood cells still contain normal levels of hemoglobin but their distorted shapes and inelastic and damaged membranes may be keeping them from delivering normal amounts of oxygen to the cells.

The red blood cell issues and Shungu’s findings suggesting that narrowed blood vessels are creating a hypoxic or low oxygen environment in the brain provide another possible way to explain for the low energy problems in ME/CFS.

Three more grants by the Open Medicine Foundation and Ron Davis will attempt to further characterize the red blood issues in ME/CFS with an eye to producing a cost-effective biomarker.

Could the microvascular system – the small capillaries and the red blood cells that run through them – hold the key to energy problems in chronic fatigue syndrome (ME/CFS) and perhaps fibromyalgia? The idea that the blood delivery system – not some metabolic derangement per se – is causing the problems with energy production is not new...
 
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Thank you for posting this article, @Eagles.

Would this RBC abnormality correlate with low ferritin in some pwME? I understand some with ME have good ferritin levels, so this won't be be universal.
 
Eagles said:
The SJSU/Stanford study overseeen by Ron Davis suggests that ME/CFS patient’s red blood cells are often no longer round

.............. their distorted shapes and inelastic and damaged membranes may be keeping them from delivering normal amounts of oxygen to the cells.
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If our red blood cells are distorted shapes and no longer round, wouldn't this show up on routine blood testing and get flagged at the time? I've never had a blood test over the past 28 years that suggested there was a problem with the shape of my red blood cells.
 
TigerLilea said:
If our red blood cells are distorted shapes and no longer round, wouldn't this show up on routine blood testing and get flagged at the time? I've never had a blood test over the past 28 years that suggested there was a problem with the shape of my red blood cells.
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It does seem like this would have been reported previously if it was visible on a routine test. Maybe this is something seen only after the cells exit a narrow channel like a capillary. If the cells are relatively inelastic, perhaps they retain their compressed shape longer after squeezing through a tight space, but eventually they return to normal appearance by the time they get to a larger vessel from which a blood sample might be taken. Just guessing.
 
TigerLilea said:
If our red blood cells are distorted shapes and no longer round, wouldn't this show up on routine blood testing and get flagged at the time? I've never had a blood test over the past 28 years that suggested there was a problem with the shape of my red blood cells.
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I've often wondered the same thing.
 
TigerLilea said:
If our red blood cells are distorted shapes and no longer round, wouldn't this show up on routine blood testing and get flagged at the time? I've never had a blood test over the past 28 years that suggested there was a problem with the shape of my red blood cells.
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When Les Simpson found deformed RBCs he did so by examining cells as soon as they were taken from the patient. AS soon as they were put into solution they became normal. He was very annoyed that people wo claimed they could not replicate his study had not done this.

Also normal blood draws are taken from large veins not capillaries so they have plenty of room so deformability wouldn't be a problem. There are not many blood tests which look at the actual RBCs; in many the cells are clotted and discarded and it is the serum that is examined
 
Full text now available, https://content.iospress.com/articles/clinical-hemorheology-and-microcirculation/ch180469
Abstract
BACKGROUND:
Myalgic encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is a poorly understood disease. Amongst others symptoms, the disease is associated with profound fatigue, cognitive dysfunction, sleep abnormalities, and other symptoms that are made worse by physical or mental exertion. While the etiology of the disease is still debated, evidence suggests oxidative damage to immune and hematological systems as one of the pathophysiological mechanisms of the disease. Since red blood cells (RBCs) are well-known scavengers of oxidative stress, and are critical in microvascular perfusion and tissue oxygenation, we hypothesized that RBC deformability is adversely affected in ME/CFS.

METHODS:
We used a custom microfluidic platform and high-speed microscopy to assess the difference in deformability of RBCs obtained from ME/CFS patients and age-matched healthy controls.

RESULTS AND CONCLUSION:
We observed from various measures of deformability that the RBCs isolated from ME/CFS patients were significantly stiffer than those from healthy controls. Our observations suggest that RBC transport through microcapillaries may explain, at least in part, the ME/CFS phenotype, and promises to be a novel first-pass diagnostic test.
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Is there any mention of the length of time that these patients were ill?

What about studying a clean slate of ME/CFS patients of long duration?

"The distributions for entry time and transit velocity are skewed towards lower values for HC and towards higher values for those for ME/CFS patients. Because of the nature of the disease, often most patients were prescribed a wide range of medications and supplements depending on their particular symptoms and condition. For instance, these medications and supplements include Rituxan and loratadine or low-dose naltrexone, Vitamin D3 etc. Based on extensive literature search, we found only one of the drugs, colchicine, which was prescribed to one patient, has been shown to slightly affect cellular deformability [15, 16]. However, the deformability parameters for this particular patient were well within the range for other patients. The patients and volunteers identified themselves as non-smokers [17]".
 
Mij said:
Is there any mention of the length of time that these patients were ill?

What about studying a clean slate of ME/CFS patients of long duration?
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The paper states they used fresh blood, so that will severely limit them to volunteers who live close to the test lab, and available at a time the researchers and their equipment are available. Once the team comes up with an easier to use test that should open the door to many different types of studies assuming funding can be found. I wonder if they can overcome the limitation of using fresh blood........... lots more research still to do.

This Les Simpson article reported more investigations regarding length of disease and changes over time in a longitudinal study. That might be of interest to you regarding length of illness @Mij
http://www.positivehealth.com/artic...-of-blood-flow-and-evening-primrose-oil-in-me
Although the majority of samples showed high percentages of cup-transformed red cells, there were small numbers of cases with high values for flat cells or cells with altered margins. During the next two years the latter changes became dominant, leading to the proposal that high values for cup forms was a marker for acute ME, while increased flat cells or cells with altered margins were indicators of chronic ME. This shift from acute to chronic status was well shown in a report of the red cell shape populations of 1558 female and 620 male members of ME organisations in New Zealand, Australia, South Africa and the UK.[10] In both sexes, high values for flat cells was the dominant change, and about 15% had no abnormal values, which suggested that they might have been in remission at the time of sampling.
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A panel of ME volunteers (37 females, 11 males) who had been diagnosed as having ME by a physician at least two years previously, agreed to meet every four weeks for forty weeks. At each meeting a blood sample was obtained and their state of health was recorded in terms of symptoms and their perceived level of wellbeing. The most striking feature of the results was the range of variability of their health problems. At one extreme, five women had abnormal values in all eleven blood samples, which were associated with severe symptoms and poor wellbeing. While it is possible that the women may have experienced remissions in the four-week interval, it is also possible that they had the non-remitting form of ME. At the other extreme was a woman who had six of her eleven samples showing normal values. When the results from both sexes were combined, the median result was to have two normal blood tests with normal wellbeing during the forty weeks of the study. On the basis of these findings, it is reasonable to conclude that remissions are not uncommon events in people with ME.
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wigglethemouse said:
Here is the meat and potatoes of the paper

View attachment 5360
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I've just received this "link to the complete version of the Red Blood Cell Deformability research paper" from OMF:
https://content.iospress.com/articl...l_Hemorheology_and_Microcirculation_TrendMD_0

From memory OMF recently expanded the team working on red cell deformability. Looks promising i.e. as a potential diagnostic test; hopefully we don't get further disappointing news [i.e. as per difficulties in measuring intracellular tryptophan].

Has anyone got access to data from Gulf War veterans? There's a reference to data from Gulf War veterans (reference "11") in this paper.
 
FMMM1 said:
I've just received this "link to the complete version of the Red Blood Cell Deformability research paper" from OMF:
https://content.iospress.com/articl...l_Hemorheology_and_Microcirculation_TrendMD_0

From memory OMF recently expanded the team working on red cell deformability. Looks promising i.e. as a potential diagnostic test; hopefully we don't get further disappointing news [i.e. as per difficulties in measuring intracellular tryptophan].

Has anyone got access to data from Gulf War veterans? There's a reference to data from Gulf War veterans (reference "11") in this paper.
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Link isn't to the same thing as the subject of this thread, yours/OMFs goes to a study with the title, "Abnormal rheological properties of red blood cells as a potential marker of Gulf War Illness: A preliminary study".
 
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