Professor emeritus Malcolm Hooper har skrevet en 442 sider lang rapport: MAGICAL MEDICINE: HOW TO MAKE A DISEASE DISAPPEAR
Det er en meget kritisk rapport over psykiateres behandling af ME/CFS med kognitiv terapi og gradueret motion.
I rapporten faldt jeg over et citat:
"Seemingly because of the Wessely School’s beliefs, children with ME/CFS have been diagnosed as having "pervasive refusal syndrome" and many have been forcibly removed from their distraught parents (see below), who themselves have been labelled as having Munchausen’s Syndrome by Proxy, a damaging label that is never deleted from their medical records."
direkte oversat: "Tilsyneladende på grund af Wessely School overbevisninger, er børn med ME/CFS blevet diagnosticeret som havende "omsiggribende afvisningssyndrom", og mange er blevet tvangsfjernet fra deres fortvivlede forældre (se nedenfor), der selv er blevet stemplet som havende Munchausen syndrom by Proxy, en ødelæggende betegnelse, som aldrig bliver slettet fra deres journaler."
Det fik mig til at kigge lidt nærmere på Pervasive Refusal Syndrome (PRS), som på dansk blot kaldes "afvisningssyndrom".
Det viser sig, at "afvisningssyndrom" ikke er diagnose kode på WHOs liste. (ME er med på WHOs liste og har diagnosekode G93.3.)
Hvis man går ind i pubmed databasen over videnskabelige artikler og søger på "Pervasive Refusal Syndrome" dukker der (i skrivende stund) kun 18 resultater op. Det må siges, at være meget, meget beskeden dokumentation for en sygdom. Til sammenligning kan det nævnes, at en søgning på "sclerosis" giver 104.472 resulater, og selv en forsker-forsømt sygdom som "myalgic encephalomyelitis" giver 6.127 resulater.
Jeg fandt en enkel dansk artikel, der beskriver fænomenet hos et enkelt barn: Afvisningssyndrom hos en 12-årig dreng
I artiklen er opstillet to eksempler på diagnosekriterier. Jeg gengiver det ene eksempel:
"A. Delvis eller total vægring ved medvirken i forhold til tre eller flere af følgende domæner: 1) spisning, 2) mobilisation, 3) tale, 4) personlig hygiejne
B. Aktiv og vredladen modstand imod støtte og opmuntring
C. Social tilbagetrækning og skolefravær
D. Ingen organisk baggrund for symptomernes sværhedsgrad
E. Ingen anden psykiatrisk diagnose dækker tilstandens karakter bedre
F. Tilstandens livstruende karakter kræver hospitalsindlæggelse."
I indledningen til denne artikel forklares, at diganosen opståen bygger på 4 tilfælde, hvor "Børnenes adfærd var ledsaget af aktiv afvisning af støtte fra familie eller personale. De ophørte med at gå, tale, spise, drikke og drage omsorg for egen hygiejne."
Længere nede i artiklen står der "De umiddelbart udløsende faktorer er hos over halvdelen infektion eller akut traume."
Jeg synes, at det lød meget mærkeligt, og tænkte "mon der kan være andet og mere på spil?" Det viser sig, at den tanke har andre også haft for i denne artikel af Barry Wright and David Beverley: Pervasive refusal syndrome står der:
"Investigation of this teenager found serological evidence of post-streptococcal infection and autoimmune antibodies to parts of the brain responsible for aspects of movement. This throws up a number of questions about whether children with conditions of this nature are a heterogenous group, whether we fully understand their aetiology and how best to provide treatment and support."
oversat:
"Undersøgelse af denne teenager viste serologiske tegn på post-streptokokinfektion og autoimmune antistoffer mod dele af hjernen, der er ansvarlige for aspekter af bevægelse. Dette stiller en række spørgsmål om, hvorvidt børn med lidelser af denne art er en heterogen gruppe, uanset om vi fuldt ud forstår deres ætiologi og hvordan man bedst kan yde behandling og støtte."
Her er det fornuftigt lige at standse op og tænke sig godt om! Hvad foregår der egentlig her?
Der er en strid mellem forskere, læger, patientforeninger og ME patienter om ME er fysisk (og måske endda en autoimmun) eller en psykisk sygdom. Hvis ME diagnosen, så erstattes af "afvisningssyndrom", og den diagnose så også er under diskussion, om den er fysisk/autoimmun eller om den er psykisk, så er vi sådan set slået tilbage til start.
På ME/CFS området er der en stribe forskellige diagnose kriterier, der diskueres i en uendelighed. En sygdom mere som afvisningssyndrom, med endnu en diskutabel liste af symptomer, som ovenikøbet kan rodes sammen med ME, er bestemt ikke på min ønskeliste.
Hvad jeg derimod godt kunne tænke mig var forskning, der kaster mere lys på autoantistoffer, der kan forårsage alvorlig fysisk sygdom, hvor der også udvises psykiske symptomer. Jeg kan varmt anbefale, at man tager sig tid til at klikke ind på denne spændende rapport af M.D., D. Sc. (Med.) Finn E. Somnier fra Statens Serum Institut:
Autoimmune encephalitis - History & current knowledge
Rapporten beskriver tydeligt alle de neuropsykiatriske og adfærdsmæssige symptomer som autoimmune tilstande kan frembringe.
lørdag den 29. juni 2013
onsdag den 26. juni 2013
Immune status of CFS patients - Immunstatus hos CFS patienter
In English - længere nede på dansk.
There has been published an interesting report "Characterization of phenotypic and functional Immune status of patients with Chronic Fatigue Syndrome" in German:
from Institute for Medicial Immunology :
I have google translated a small piece from page 49:
Our analyzes have shown that an increased incidence (approximately 11%) of autoimmune thyroiditis (Hashimoto's thyroiditis) is present in CFS patients. In contrast, the incidence of autoimmune thyroiditis in the normal population of about 1.5 -2% (ref 60). This finding suggests involvement of autoimmune processes in the pathogenesis of CFS.
In addition, a frequency in the immunological diagnosis, immunoglobulin deficiency was observed in (31%). A total of 5% of patients had an IgA deficiency, 6% a selective IgG deficiency main classes, 10% of a selective IgG3 deficiency, 10% selective IgG4 deficiency.
Der er udkommet en spændende rapport "Karakteriseringen af den fænotypiske og funktionelle Immunstatus hos patienter med Chronic Fatigue syndrome" på tysk. Jeg har google oversat en lille "godbid" fra side 49:
Vores analyser har vist, at en øget forekomst (ca. 11%) af autoimmun thyroiditis (Hashimotos thyroiditis) er til stede i CFS patienter. I modsætning hertil er forekomsten af autoimmun thyroiditis i den normale befolkning på omkring 1,5 -2% (ref 60). Dette fund tyder på involvering af autoimmune processer i patogenese af CFS.
Desuden er en hyppighed i den immunologiske diagnose, Immunoglobulin mangel, blevet observeret i (31%). I alt 5% af patienterne havde en IgA-mangel, 6% en selektiv IgG mangel hovedklasser, 10% af en selektiv IgG3 mangel, 10% selektiv IgG4 mangel.
Vielen dank an Dr. med. Michael Knops!!!
There has been published an interesting report "Characterization of phenotypic and functional Immune status of patients with Chronic Fatigue Syndrome" in German:
from Institute for Medicial Immunology :
I have google translated a small piece from page 49:
Our analyzes have shown that an increased incidence (approximately 11%) of autoimmune thyroiditis (Hashimoto's thyroiditis) is present in CFS patients. In contrast, the incidence of autoimmune thyroiditis in the normal population of about 1.5 -2% (ref 60). This finding suggests involvement of autoimmune processes in the pathogenesis of CFS.
In addition, a frequency in the immunological diagnosis, immunoglobulin deficiency was observed in (31%). A total of 5% of patients had an IgA deficiency, 6% a selective IgG deficiency main classes, 10% of a selective IgG3 deficiency, 10% selective IgG4 deficiency.
Der er udkommet en spændende rapport "Karakteriseringen af den fænotypiske og funktionelle Immunstatus hos patienter med Chronic Fatigue syndrome" på tysk. Jeg har google oversat en lille "godbid" fra side 49:
Vores analyser har vist, at en øget forekomst (ca. 11%) af autoimmun thyroiditis (Hashimotos thyroiditis) er til stede i CFS patienter. I modsætning hertil er forekomsten af autoimmun thyroiditis i den normale befolkning på omkring 1,5 -2% (ref 60). Dette fund tyder på involvering af autoimmune processer i patogenese af CFS.
Desuden er en hyppighed i den immunologiske diagnose, Immunoglobulin mangel, blevet observeret i (31%). I alt 5% af patienterne havde en IgA-mangel, 6% en selektiv IgG mangel hovedklasser, 10% af en selektiv IgG3 mangel, 10% selektiv IgG4 mangel.
Vielen dank an Dr. med. Michael Knops!!!
mandag den 17. juni 2013
TRPA1 og Multiple Chemical Sensitivity
Jeg har tidligere skrevet om TRPA1 og MCS: Transient Receptor Potential in Multiple Chemical Sensitivity
Og jeg har gættet på et lille forsøg, som kunne være interessant: Kan mRNA for TRPA1 benyttes som biomarkør for MCS?
Og nu fandt jeg lige ud af, at andre længe før mig har haft lignende tanker, dog ikke i forbindelse med MCS, men i forbindelse med Gulf War Illness (GWI). Disse krigsveteraner har været eksponeret for mange kemikalier og en stor del af dem har udviklet kemikalieoverfølsomhed. Professor Bruce Zuraw er manden bag et forsøg med titlen Epithelial Cell TRPV1-Mediated Airway Sensitivity as a Mechanism for Respiratory Symptoms Associated with Gulf War Illness
Han vil finde ud af om TRPV1 og TRPA1 er opreguleret hos GWI veteraner og om dette kan anvendes i forbindelse med en biomarkør. I forsøgsbeskrivelsen kan man læse følgende:
"We propose that the respiratory symptoms of subjects with GWI is caused in part by enhanced airway sensitivity to irritants, mediated primarily by upregulated or sensitized TRP channels in the airway. We have now shown that transformed and primary airway epithelial cells express functional TRPV1. More recently we found that these cells also express another important irritant receptor, namely TRPA1. Activation of either TRPV1 or TRPA1 results in increased expression of both the inflammatory cytokine IL-8 and the neurotrophin NGF in airway epithelial cells. We have further shown that NGF as well as bradykinin and CCL5 can sensitize TRPV1, lower the activation threshold, and enhance the inflammatory consequences of agonist stimulation. The combination of sensitized TRPV1 channels that have a lower threshold for activation from common irritants combined with TRP activation-mediated synthesis of NGF leading to further sensitization of sensory afferents and epithelial cells suggests a mechanism by which non-specific airway sensitivity may be initiated and sustained in a self-perpetuating manner."
og længere nede:
"As detailed above, we have developed sensitive real-time RT-PCR assays for mRNA transcripts of these genes, including TRPV1, TRPA1, the bradykinin B2 and B1 receptors, the entire range of neurotrophin receptors, and the cannabinoid receptor, CNR2. We still need to design and test primers for the tachykinin receptors."
Jeg tror næppe, at aktiverede TRPV1 og TRPA1 receptorer (målt ved mRNA eller ander metoder) kan stå alene som biomarkør for respiratoriske problemer eller MCS. Men sammen med andre parametre kunne det være en mulighed. Under alle omstændigheder er det forsøg som disse, der vil kaste mere lys på biokemien bag ved sygdomme som GWI og MCS.
Andre forskere spekulerer allerede i hvordan respiratoriske tilstande, herunder MCS, kan behandles med TRPA1 antagonister. Se denne patentansøgning:
PHARMACEUTICAL COMPOSITION COMPRISING A TRPA1 ANTAGONIST AND AN ANTICHOLINERGIC AGENT
"The present patent application relates to a pharmaceutical composition comprising a transient receptor potential ankyrin-1 receptor ("TRPA1") antagonist and an anticholinergic agent. Particularly, the application provides a pharmaceutical composition comprising a TRPA1 antagonist having IC50 for inhibiting human TRPA1 receptor activity of less than 1 micromolar and an anticholinergic agent; a process for preparing such composition; and its use in treating a respiratory disorder in a subject."
"The respiratory disorder, in the context of present invention, includes but is not limited to airway inflammation, asthma, emphysema, bronchitis, COPD, sinusitis, rhinitis, cough, respiratory depression, reactive airways dysfunction syndrome (RADS), acute respiratory distress syndrome (ARDS), irritant induced asthma, occupational asthma, sensory hyper-reactivity, multiple chemical sensitivity, and aid in smoking cessation therapy."
Og jeg har gættet på et lille forsøg, som kunne være interessant: Kan mRNA for TRPA1 benyttes som biomarkør for MCS?
Og nu fandt jeg lige ud af, at andre længe før mig har haft lignende tanker, dog ikke i forbindelse med MCS, men i forbindelse med Gulf War Illness (GWI). Disse krigsveteraner har været eksponeret for mange kemikalier og en stor del af dem har udviklet kemikalieoverfølsomhed. Professor Bruce Zuraw er manden bag et forsøg med titlen Epithelial Cell TRPV1-Mediated Airway Sensitivity as a Mechanism for Respiratory Symptoms Associated with Gulf War Illness
Han vil finde ud af om TRPV1 og TRPA1 er opreguleret hos GWI veteraner og om dette kan anvendes i forbindelse med en biomarkør. I forsøgsbeskrivelsen kan man læse følgende:
"We propose that the respiratory symptoms of subjects with GWI is caused in part by enhanced airway sensitivity to irritants, mediated primarily by upregulated or sensitized TRP channels in the airway. We have now shown that transformed and primary airway epithelial cells express functional TRPV1. More recently we found that these cells also express another important irritant receptor, namely TRPA1. Activation of either TRPV1 or TRPA1 results in increased expression of both the inflammatory cytokine IL-8 and the neurotrophin NGF in airway epithelial cells. We have further shown that NGF as well as bradykinin and CCL5 can sensitize TRPV1, lower the activation threshold, and enhance the inflammatory consequences of agonist stimulation. The combination of sensitized TRPV1 channels that have a lower threshold for activation from common irritants combined with TRP activation-mediated synthesis of NGF leading to further sensitization of sensory afferents and epithelial cells suggests a mechanism by which non-specific airway sensitivity may be initiated and sustained in a self-perpetuating manner."
og længere nede:
"As detailed above, we have developed sensitive real-time RT-PCR assays for mRNA transcripts of these genes, including TRPV1, TRPA1, the bradykinin B2 and B1 receptors, the entire range of neurotrophin receptors, and the cannabinoid receptor, CNR2. We still need to design and test primers for the tachykinin receptors."
Jeg tror næppe, at aktiverede TRPV1 og TRPA1 receptorer (målt ved mRNA eller ander metoder) kan stå alene som biomarkør for respiratoriske problemer eller MCS. Men sammen med andre parametre kunne det være en mulighed. Under alle omstændigheder er det forsøg som disse, der vil kaste mere lys på biokemien bag ved sygdomme som GWI og MCS.
Andre forskere spekulerer allerede i hvordan respiratoriske tilstande, herunder MCS, kan behandles med TRPA1 antagonister. Se denne patentansøgning:
PHARMACEUTICAL COMPOSITION COMPRISING A TRPA1 ANTAGONIST AND AN ANTICHOLINERGIC AGENT
"The present patent application relates to a pharmaceutical composition comprising a transient receptor potential ankyrin-1 receptor ("TRPA1") antagonist and an anticholinergic agent. Particularly, the application provides a pharmaceutical composition comprising a TRPA1 antagonist having IC50 for inhibiting human TRPA1 receptor activity of less than 1 micromolar and an anticholinergic agent; a process for preparing such composition; and its use in treating a respiratory disorder in a subject."
"The respiratory disorder, in the context of present invention, includes but is not limited to airway inflammation, asthma, emphysema, bronchitis, COPD, sinusitis, rhinitis, cough, respiratory depression, reactive airways dysfunction syndrome (RADS), acute respiratory distress syndrome (ARDS), irritant induced asthma, occupational asthma, sensory hyper-reactivity, multiple chemical sensitivity, and aid in smoking cessation therapy."
A small peculiarity - ME, "ciguatoxin-look-alike" and TRPA1
I fell upon a small peculiarity regarding my favorite ion channel, TRPA1.
Some years ago a group of researchers pointet out, that the clinical symptoms found in both Chronic Fatigue Syndrome (CFS) and chronic Ciguatera fish poisoning (CCFP) were remarkably similar, including recurrent fatigue, impaired memory and concentration, tender lymph nodes, muscle and joint pain, headaches, and other neurological impairments.
They perfermed a study and found that the serum lipid fraction of patients with CFS has a structural epitope(s) similar to ciguatoxin CTX, a polyether lipid with neurotoxic properties produced by a marine organism (Gambierdiscus toxicus).
Ciguatoxins are sodium channel activator toxins that cause ciguatera, which presents with peripheral sensory disturbances, including the symptom of cold allodynia which is characterized by intense stabbing and burning pain in response to mild cooling.
And now for the peculiarity: Ciguatoxins activate specific cold pain pathways to elicit the burning pain from cooling, and TRPA1 is involved in this pathway.
References:
Acute Phase Phospholipids Related to the Cardiolipin of Mitochondria in the Sera of Patients With Chronic Fatigue Syndrome (CFS), Chronic Ciguatera Fish Poisoning (CCFP), and Other Diseases Attributed to Chemicals, Gulf War, and Marine Toxins
Ciguatoxins activate specific cold pain pathways to elicit burning pain from cooling
If you are up for one more peculiarity..the author, Yoshitsugi Hokama, from the Acute Phase Phospholipid article is also on this paper about CFS, phospholipid cardiolipin (CL) and anticardiolipin antibodies (ACAs): Anticardiolipin Antibodies in the Sera of Patients with Diagnosed Chronic Fatigue Syndrome
..and I quote:
"This study demonstratesthat a large percentage of patients clinically diagnosed with CFS have elevated levels of the IgM isotype to CL (95%), suggesting that CFS may be an autoimmune condition."
"Previous studies have shown that treatment with monoclonal antibodies to B cells reduces ACA levels to normal in patients with autoimmune disease, leading to clinical improvements."
Some years ago a group of researchers pointet out, that the clinical symptoms found in both Chronic Fatigue Syndrome (CFS) and chronic Ciguatera fish poisoning (CCFP) were remarkably similar, including recurrent fatigue, impaired memory and concentration, tender lymph nodes, muscle and joint pain, headaches, and other neurological impairments.
They perfermed a study and found that the serum lipid fraction of patients with CFS has a structural epitope(s) similar to ciguatoxin CTX, a polyether lipid with neurotoxic properties produced by a marine organism (Gambierdiscus toxicus).
Ciguatoxins are sodium channel activator toxins that cause ciguatera, which presents with peripheral sensory disturbances, including the symptom of cold allodynia which is characterized by intense stabbing and burning pain in response to mild cooling.
And now for the peculiarity: Ciguatoxins activate specific cold pain pathways to elicit the burning pain from cooling, and TRPA1 is involved in this pathway.
References:
Acute Phase Phospholipids Related to the Cardiolipin of Mitochondria in the Sera of Patients With Chronic Fatigue Syndrome (CFS), Chronic Ciguatera Fish Poisoning (CCFP), and Other Diseases Attributed to Chemicals, Gulf War, and Marine Toxins
Ciguatoxins activate specific cold pain pathways to elicit burning pain from cooling
If you are up for one more peculiarity..the author, Yoshitsugi Hokama, from the Acute Phase Phospholipid article is also on this paper about CFS, phospholipid cardiolipin (CL) and anticardiolipin antibodies (ACAs): Anticardiolipin Antibodies in the Sera of Patients with Diagnosed Chronic Fatigue Syndrome
..and I quote:
"This study demonstratesthat a large percentage of patients clinically diagnosed with CFS have elevated levels of the IgM isotype to CL (95%), suggesting that CFS may be an autoimmune condition."
"Previous studies have shown that treatment with monoclonal antibodies to B cells reduces ACA levels to normal in patients with autoimmune disease, leading to clinical improvements."
fredag den 14. juni 2013
Caveolae, eNOS and TRPA1?
I have followed a chain of thought and I wonder if there is a connection. What do you think? Do these puzzle pieces fit together or maybe just some of them?
The short version: Some ME patients have POTS. Some POTS patients may have autoantibodies against cavin-1. Cavin-1 is required for the formation of caveolae. Regulation of eNOS within caveolae is an important mechanism. eNOS activation leads to high levels of NO in cells. NO-/HNO can activate TRPA1 receptors. TRPA1 is involved in many mechanisms....for example "TRPA1 is involved in mediating vasodilation. TRPA1 can also influence changes in blood pressure of possible relevance to autonomic system reflexes and potentially to vasovagal/neurocardiogenic syncope disorders."
The long version:
Postural orthostatic tachycardia syndrome is an under-recognized condition in chronic fatigue syndrome.
Link to picture of caveolae
A newly described protein, cavin-1, also known as polymerase I and transcript release factor, is one of the targets of the autoantibodies in POTS. Cavin-1 is required for the formation of caveolae in all mammalian and plays a critical role in regulating caveolae function in endothelial cells.
Reference: Autoimmunoreactive IgGs against cardiac lipid raft-associated proteins in patients with postural orthostatic tachycardia syndrome
In terms of endothelial cell function, caveolae function, caveolae are important regulators of vascular tone through modulation of endothelial nitric oxide synthase (eNOS) activity. Specifically, regulation of eNOS within caveolae by the coat protein, caveolin-1 (Cav-1), is an important physiological mechanism for control of vascular reactivity, and this pathway is intimately involved with the progression of pathologies likely through suppression of pro-inflammatory signalling pathways.
The relationship between caveolae and eNOS is one of the cornerstones of caveolae involvement in cardiovascular function. Loss of Cav-1 leads to persistent eNOS activation and high levels of NO in cells through the loss of Cav-1 inhibitory effect on eNOS. The Cav-1/eNOS interaction tonically inhibits eNOS activity resulting in sequestering of eNOS in caveolae and reduced NO production.
Reference: Caveolae, caveolins, and cavins: complex control of cellular signalling and inflammation
Link to picture of regulation of eNOS in caveolae
NO-/HNO can increase meningeal blood flow by activating TRPA1 receptors, most likely through stimulation of CGRP release from meningeal afferents. Similar mechanisms may be involved in the pathophysiology of headaches associated with the endogenous NO metabolism.
Reference: Involvement of TRPA1 receptors in meningeal blood flow induced by formation of nitroxyl (NO-/HNO)
Previous posts about TRP channels:
Once again: TRPA1! Is activation of TRPA1 involved in ME?
Kan mRNA for TRPA1 benyttes som biomarkør for MCS?...
Puslespilsbrikkerne: LPS, TLR4, TRPA1 og ME!?!
Vedvarende aktivering af TRPA1 og aflastning?
Variation i sensoriske reaktioner, TRP og stress
TRPA1, muskelaktivitet og påvirkning af det autono...
ME, slow gastric emptying, serotonin and TRPA1
TRPA1, Hypoxia and ME?
Mitochondrial dysfunction - influence on TRPA1
Exercise and...TRPA1 and TRPV1
ME, neuropathy, TRPA1
TRPA1 involvement in autonomic dysfunction in ME?
TRPA1/TRPV4/PAR in inflammation/pain
Transient Receptor Potential in Multiple Chemical ...
TRP Ion Channels
The short version: Some ME patients have POTS. Some POTS patients may have autoantibodies against cavin-1. Cavin-1 is required for the formation of caveolae. Regulation of eNOS within caveolae is an important mechanism. eNOS activation leads to high levels of NO in cells. NO-/HNO can activate TRPA1 receptors. TRPA1 is involved in many mechanisms....for example "TRPA1 is involved in mediating vasodilation. TRPA1 can also influence changes in blood pressure of possible relevance to autonomic system reflexes and potentially to vasovagal/neurocardiogenic syncope disorders."
The long version:
Postural orthostatic tachycardia syndrome is an under-recognized condition in chronic fatigue syndrome.
Link to picture of caveolae
A newly described protein, cavin-1, also known as polymerase I and transcript release factor, is one of the targets of the autoantibodies in POTS. Cavin-1 is required for the formation of caveolae in all mammalian and plays a critical role in regulating caveolae function in endothelial cells.
Reference: Autoimmunoreactive IgGs against cardiac lipid raft-associated proteins in patients with postural orthostatic tachycardia syndrome
In terms of endothelial cell function, caveolae function, caveolae are important regulators of vascular tone through modulation of endothelial nitric oxide synthase (eNOS) activity. Specifically, regulation of eNOS within caveolae by the coat protein, caveolin-1 (Cav-1), is an important physiological mechanism for control of vascular reactivity, and this pathway is intimately involved with the progression of pathologies likely through suppression of pro-inflammatory signalling pathways.
The relationship between caveolae and eNOS is one of the cornerstones of caveolae involvement in cardiovascular function. Loss of Cav-1 leads to persistent eNOS activation and high levels of NO in cells through the loss of Cav-1 inhibitory effect on eNOS. The Cav-1/eNOS interaction tonically inhibits eNOS activity resulting in sequestering of eNOS in caveolae and reduced NO production.
Reference: Caveolae, caveolins, and cavins: complex control of cellular signalling and inflammation
Link to picture of regulation of eNOS in caveolae
NO-/HNO can increase meningeal blood flow by activating TRPA1 receptors, most likely through stimulation of CGRP release from meningeal afferents. Similar mechanisms may be involved in the pathophysiology of headaches associated with the endogenous NO metabolism.
Reference: Involvement of TRPA1 receptors in meningeal blood flow induced by formation of nitroxyl (NO-/HNO)
Previous posts about TRP channels:
Once again: TRPA1! Is activation of TRPA1 involved in ME?
Kan mRNA for TRPA1 benyttes som biomarkør for MCS?...
Puslespilsbrikkerne: LPS, TLR4, TRPA1 og ME!?!
Vedvarende aktivering af TRPA1 og aflastning?
Variation i sensoriske reaktioner, TRP og stress
TRPA1, muskelaktivitet og påvirkning af det autono...
ME, slow gastric emptying, serotonin and TRPA1
TRPA1, Hypoxia and ME?
Mitochondrial dysfunction - influence on TRPA1
Exercise and...TRPA1 and TRPV1
ME, neuropathy, TRPA1
TRPA1 involvement in autonomic dysfunction in ME?
TRPA1/TRPV4/PAR in inflammation/pain
Transient Receptor Potential in Multiple Chemical ...
TRP Ion Channels
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