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vrijdag 29 april 2011

LDN de juiste keuze

Voor degenen die de blog al een tijdje volgen, jullie weten dat ik Low Dose Naltrexone (LDN) gebruik om te genezen.
Het mechanisme achter de LDN vind je grotendeels terug op de aparte pagina op deze blog.

Belangrijk is te begrijpen dat ME/CVS onder meer een neurologische aandoening is met immunologische gevolgen. Dankzij een intelligent persoon, kan ik vandaag mijn verstand weer deels gebruiken en is de recuperatietijd na een inspanning verkort. Tevens heeft hij mijn visie op het functioneren van de mens verduidelijkt.

De oorzaak van deze neurologische verstoring ligt in de endorfine receptoren. Die vervullen een heleboel functies.
Deze receptoren zijn afhankelijk van wat je eet en welke enzymen dit voedsel afbreken. Als er daar iets misloopt, zit je in de problemen. Net zo'n specifiek enzym (DPP IV) is verbonden met neuropeptide Y dat nu geciteerd is in een onderzoek als cruciaal in chronische pijn (bv fibromyalgie).

Hetzelfde enzym kwam ook ter sprake op de NIH workshop van 7 & 8 april jl. tijdens de samenvatting van Dr Nancy Klimas over het werk van Broderick. Ditmaal met de duidelijke boodschap dat het een sleutelrol speelt in immuniteit, meer bepaald in het signaliseringsproces van lymfocyten.

Mijn genezingsproces zit dus op het juiste pad. Afblijven van de exorfinen - dit zijn natuurlijke opiaten - (gluten = brood, pasta, koekjes e.d., caseine = melkprodukten, soya en spinazie) en voortdoen met de LDN!

LDN stimuleert de aanmaak van nieuwe endorfine-receptoren in mijn brein, dus mijn hersenen kunnen weer werken.
En mijn brein is de computer van mijn lichaam ...
Het weet beter dan welke specialist ook wat er moet gerepareerd worden.

Een chronisch ziek lichaam genezen is zoals een oud huis repareren. Veel kosten en oude rommel eruit. Zwoegen, zweten en afzien.
Maar beetje bij beetje wordt het mooier en beter.

Tonic inhibition of chronic pain by neuropeptide Y

Brian Solwaya,b, Soma C. Boseb, Gregory Corderb, Renee R. Donahueb, and Bradley K. Taylora,b,1
+ Author Affiliations

aNeuroscience Graduate Program, Tulane University Health Sciences Center, New Orleans, LA 70112; and bDepartment of Physiology, School of Medicine, University of Kentucky Medical Center, Lexington, KY 40536
Edited* by Tomas G. M. Hökfelt, Karolinska Institutet, Stockholm, Sweden, and approved March 14, 2011 (received for review November 30, 2010)


Dramatically up-regulated in the dorsal horn of the mammalian spinal cord following inflammation or nerve injury, neuropeptide Y (NPY) is poised to regulate the transmission of sensory signals. We found that doxycycline-induced conditional in vivo (Npytet/tet) knockdown of NPY produced rapid, reversible, and repeatable increases in the intensity and duration of tactile and thermal hypersensitivity.

Remarkably, when allowed to resolve for several weeks, behavioral hypersensitivity could be dramatically reinstated with NPY knockdown or intrathecal administration of Y1 or Y2 receptor antagonists. In addition, Y2 antagonism increased dorsal horn expression of Fos and phosphorylated form of extracellular signal-related kinase.

Taken together, these data establish spinal NPY receptor systems as an endogenous braking mechanism that exerts a tonic, long-lasting, broad-spectrum inhibitory control of spinal nociceptive transmission, thus impeding the transition from acute to chronic pain. NPY and its receptors appear to be part of a mechanism whereby mammals naturally recover from the hyperalgesia associated with inflammation or nerve injury.

PS: Pijnstillers van de opiatenfamilie maken dezelfde receptoren kapot dus afblijven als je immuunsysteem je lief is! Als de pijn niet te harden of chronisch is, vraag aan je arts Celebrex, Topamax, Normast, ... en eet zo natuurlijk mogelijk zonder de exorfinen. Je kan ook het supplement D-phenylalaline bijnemen (zie pag supplementen).

Meer info over exorfinen, gluten, neuropeptide y en Low Dose Naltrexone (LDN):

67 percent of Dr. Baraniuk’s chronic migraine patients have CFS

Dr. James Baraniuk, Assistant Professor of Medicine, Georgetown University

Accompanying Document: CFS Research: Transition from the Qualitative Consensus Tradition to a Quantitative, Translational, Hypothesis-Driven, Systems Biology Strategy

Dr. Baraniuk opened his presentation by saying that he was moved to be giving his presentation in the John Eisenberg Memorial Lecture Room. Dr. Eisenberg was the department chairman at Georgetown University and the professor who gave Dr. Baraniuk his start in clinical research.

One of the things that Dr. Eisenberg encouraged was thinking out of the box. Those in CFS have to make a change from the qualitative approach and consensus tradition toward a hypothesis-based type of investigation and new methods, said Dr. Baraniuk. The bywords now are using a “systems biology” or overall approach as to what is going on in multiple areas within an individual.

He gave the example of a patient evaluation that compares pain symptoms (headache, myalgia, arthralgia, sore throat, tender lymph nodes) and psychoneural symptoms (cognitive memory problems, sleep disturbances, exertional exhaustion) with fatigue.

The hypothesis: The sum for the minor criteria will be proportional to the level of fatigue. Significant fatigue for the diagnosis was defined as moderate (3) or severe (4).

Taking the sum of the minor criteria and comparing it with significant fatigue split the population into normal subjects, those with chronic idiopathic fatigue (CIF), and those with CFS. There was no difference by age or gender. Using the sum of minor criteria was superior to using SF-36 to separate the controls, those with CIS, and those with CFS. The implications for quantification of CFS criterion severities:

Scoring the severity of each CFS criterion provides more information about each individual.

The sum of the minor criteria correlates with fatigue and is a good predictor of CFS.

The next step is to explore whether cluster or multivariate analysis will identify subsets of CFS subjects in order to find out if there are common mechanisms that are creating subsets of CFS patients. Dr. Baraniuk said that he wants to use the current grant to find objective markers that will go along with those potential subsets. The grant (RO1 ES-015382) is funded by the National Institute of Environmental Health Sciences (NIEHS).

Researchers are:

Doing lumbar punctures in 50 CFS and 50 control subjects to analyze the proteomics of the cerebrospinal fluid.

Making psychometric comparisons using a lengthy questionnaire

Making pain comparisons using dolorimetry, isometric hand grip studies, and capsaicin skin tests for neurogenic inflammation.

A problem encountered during the study was spinal headaches, which are very severe and occur after a lumbar puncture. With the idea of making lemons out of lemonade, researchers decided to see what could be learn from spinal headaches about CFS pathology. Researchers discovered that 88 percent of CFS subjects had migraines. In checking the literature, researchers found that 84 percent of the migraine populations report fatigue. In fact, 67 percent of Dr. Baraniuk’s chronic migraine patients have CFS. This statistic suggests that there is more than a chance relationship and that perhaps there is a mechanism that is shared.

Migraines plus CFS suggests:

Autonomic abnormalities

Neurogenic inflammation

very likely contribute to the high level of overlap between migraines and CFS. From a treatment perspective, if you identify migraines in 88 percent of your CFS people, you should get them started on appropriate therapy.

From this we wanted to look more at the autonomic nervous system.

The hypothesis: Autonomic control during isometric hand grip maneuvers will be dysfunctional in CFS but not in healthy controls.

Subjects squeezed a hand strain gauge as hard as they could.

Researchers measured blood pressure, heart rate, and nasal dimensions (surrogates of sympathetic nervous system vasoconstriction) during a restful “SHAM” contraction.

Subjects squeezed a hand strain gauge at 30 percent of maximum for as long as they could; researchers determined autonomic responses.

There is something called the muscle reflex. When muscles are activated, nerves stimulate the brain stem and the brain stem stimulates the sympathetic nervous system centers, which send out messages that work to increase blood flow to the local contracting muscle. The dynamics of the squeeze and release of the hand grip stimulate multimodal Type C neurons. We used to think that these neurons would have just one sensory receptor and would mediate just one sensation.

Now it’s apparent that they have a wide variety of receptors, especially the multi-modal neurons. It turns out that the acid that’s released in the muscle will activate the acid ion channel that then leads to great up regulation of the sensitivity of the TRPV, which depolarizes the nerves and sends an incredibly strong pain message to the brain. In turn, that leads to sympathetic discharge of a variety of chemicals, one of which is ATP, which if it’s released in the local muscle area, will have a positive feedback effect increasing the pain.

When you stimulate the sympathetic nervous system, you actually squeeze down on the blood vessels in your nose and as a result, you have an increase in nasal patency. This turns out to be a good measure of autonomic function or in the case of CFS, dysfunction.

Isometric Hand Grip in CFS

Controls had slightly higher maximum muscle strength, equivalent duration of muscle contractions, and similar pain scores. Researchers expected that the CFS people would have higher pain scores.

As far as the autonomic component was concerned, the first factor that changes during a contraction is that the diastolic blood pressure begins to increase. That’s also the measure that goes up the highest in the healthy controls. There’s a very significant difference between the controls and the CFS people.

The systolic blood pressure goes up next, but usually very late in the contraction, and similarly, the heart rate goes up fairly late.

As far as the nose goes, the cross-sectional area for air flow also goes up in the controls significantly greater than in the CFS people. In CFS there’s a group that has a swelling of their mucosa when they should be constricting.

Conclusion: Mucosal and systemic sympathetic reflexes are dysfunctional in the pathogenesis of CFS and the nonallergic rhinitis of CFS. The primary defect is apparently autonomic dysregulation in the brain stem.

"It’s all in your head.” That’s now the mission statement for our laboratory,” said Dr. Baraniuk. “It’s all in your head because that’s where most of your nerves are. And that’s where the problem lies, I believe.”

“That led to our approach to look at cerebral spinal fluid. By way of review, you have blood flowing into a central structure in the center of the brain. As that blood flows through that structure, you have a very carefully generated fluid produced—the cerebral spinal fluid. It surrounds the brain, circulates throughout the day, goes down your spinal column, and we can collect it by doing a lumbar puncture.”

Hypothesis: Central nervous system dysfunction is a critical component of CFS and related syndromes such as FM, Persian Gulf War Illness, multiple chemical sensitivity, irritable bowel and bladder syndromes, and other allied conditions. Analysis of the fluid flowing from the brain will identify factors that may indicate the pathology of CFS to direct the creation of new treatments, and serve as diagnostic biomarkers for future testing.

Researchers obtained cerebrospinal fluid from Gulf War Illness (GWI) subjects (most also had CFS), FM subjects (many had CFS), and control subjects for a total of 62 subjects. Researchers compared pooled samples from GWI, pooled samples from CFS, and pooled samples from controls. The identified the proteins that were only present in the GWI and CFS people. They also took individual specimens from the CFS and GWI people and compared them to individual specimens from control subjects.

Dr. Baraniuk: It was mind boggling because we ended up with about 10 proteins that were present only in our CFS group and not present in the control group. The odds of this are about 10 to the minus 15. We’re currently doing the proteomic analysis using a high-end orbitrap mass spectrometer to see if we get the same pattern. The key proteins from the CFS-related proteome, I think, give us some potential clues as to what’s going on (chart from presentation slide):

CFS – related Proteome (set of proteins)

Protease – Antiprotease Imbalance


Orosomucoid 1 and 2

Structural Injury

Amyloid APLP1

C4B (C3)

Gelsolin (apoptosis)

Oxidant Injury


Carnosine dipeptidase 1

Vascular Dysregulation


Pigment Epithelium Derived Factor (EPDF)

Vasoconstrction (ischemia)

Endothelial proliferation (repair)

Leptomeningeal Activation

Keratins 4, 10, 16, 17

Structural Repair

Brain-enhanced hyaluronan binding (BEHAB)

With the new spectrometer, researchers get about 100 times more ions per run, 100 times more peptides, and about 20 times more proteins per run. We haven’t broken the code on the patient diagnosis in order to stay unbiased, so we don’t know what the mix of controls versus CFS is in the first two-dozen samples. A total of 4,075 were identified in the 24 samples.

The orbitrap system has really dropped down the level of sensitivity so that we’re picking up a lot of proteins that we could not pick up previously. We have over 200 unique proteins from these 24 samples. We had a large number of adhesion markers and it will take awhile to sort through the many different names that appear when you start doing the bioinformatic searches. After the next batch, we’ll probably be able to start doing quantitative analysis to compare the abundance of proteins between our CFS and control group.

We’re making progress—we’re getting there. Although this started out with some people thinking that it would be just a blind hog searching for acorns, I felt that we would find specific illness-related proteins. Now, based upon the distribution the types of proteins that we’ve found, we’ve been able to extend our work into other grants in other areas where we’re currently funded and are starting, for instance, a clinical treatment trial that I hope to adapt to CFS.

Committee Discussion

Dr. Baraniuk: It’s important for all of these that we identify by mass spectrometry to go on and do a quantitative assay. For all the proteins, we have that work to do once we identify which ones are significantly different. Specifically for the cytokines, we’re comparing plasma and cerebral spinal fluid.

Dr. Klimas: Are you looking for any pathogens?

Dr. Baraniuk: In the previous study we searched for all bacteria and all viruses and found one protein. But is was not a viral protein.

Snapshots van de NIH workshop ME/CFS

Hieronder een reeks links van fragmenten uit de NIH workshop over ME/CFS die onlangs plaatsvond:
Analyse van de workshop
Samenwerking is nodig
From bed to bench ipv bench to bed
Fietstesten standardiseren en kostenplaatje
Hoe vermoeidheid meten?
Hoe gaan we patienten onderverdelen in groepen?
Dysautonomie is een biomarker in ME/CVS

De transciptie van de eerste dag staat nu ook online!


De voordelen van het eten van rode druiven (van bio-cultuur) of het nemen van het supplement  resveratrol:
- verbetert de insulineresistentie (wat ook interessant is voor mensen met een te hoge cholesterol want weefsel dat slecht reageert op insuline zal een verstoorde vethuishouding krijgen)
- zou kanker, hartziekten en dementie kunnen vermijden
- is dus goed nieuws voor mensen die aan diabetes of een metabole ziekte lijden

Van belang voor ME/CVS patienten: het heeft bewezen de levensduurte te verlengen door de risico's verbonden aan chronische inflammatie te doen dalen.

In a separate body of research, scientists determined that a 10 mg daily dose of resveratrol was associated with lowered insulin resistance in Type-II diabetics.

Resveratrol is a powerful protective anti-fungal compound found in the skin of red grapes. Known to activate a longevity signaling gene (SIRT-1), resveratrol has been shown to extend lifespan by lowering the risks associated with systemic inflammation.
The polyphenol may help to prevent cancer development, cardiovascular disease and dementia, and it is now shown to impede the development of diabetes by regulating insulin sensitivity.