Altered neuro-endocrineâimmune pathways in the irritable bowel syndrome: the top-down and the bottom-up model
Cristina Stasi ⢠Massimo Rosselli ⢠Massimo Bellini ⢠Giacomo Laffi ⢠Stefano Milani
"The mucosal mast cells are important elements in the pathogenesis of IBS [72] (Fig. 1). Barbara et al. [73] identified and quantified immunohistochemically colonic mucosal mast cells in comparison to controls.
They demonstrated that mast cells in close proximity to nerves significantly correlated with the severity and frequency of abdominal pain/discomfort. The degranulation of mast cells occurs not only in response to allergens, but also to stress, following the release of NY from sympathetic terminals [51].
Mucosal mast cells can increase mucosal permeability, thus modifying the microbiota with subsequent immune activation of the mucosa. Low grade inflammation-immune activation has been suggested to be one of the most important mechanisms of brainâgut interaction [74].
This effect has been attributed to the influence of interleukins (IL-1b, TNF-a and IL-6) in the development of motor dysfunction, visceral pain and psychological disorders, mediated by the CNS."
https://webaigo.it/download/30062013150255_pubblicazione_soci_neuroendocrine%2520pathways.pdf
Mast Cells in Stress, Pain, Blood-Brain Barrier, Neuroinflammation and Alzheimerâs Disease
Duraisamy Kempuraj, et.al.
"Mast cell activation plays an important role in stress-mediated disease pathogenesis. Chronic stress cause or exacerbate aging and age-dependent neurodegenerative diseases.
The severity of inflammatory diseases is worsened by the stress. Mast cell activation-dependent inflammatory mediators augment stress associated pain and neuroinflammation.
Stress is the second most common trigger of headache due to mast cell activation.
Mast cells are associated with inflammation and pain. Stress conditions can activate mast cells and augment neuroinflammation through the activation of glial cells and neurons.
Stress can induce HPA activation and mast cell activation that lead to neuroinflammation, BBB disruption and tight junction damage in the brain.
Stress can induce the generation of APP, hyperphosphorylation of tau, NFTs, Aβ peptide, APs, oxidative stress, cognitive dysfunction, synaptic loss, neuronal loss, inflammatory mediator expression, and dementia in AD pathogenesis. "
Corticotropin-Releasing Hormone and Brain Mast Cells Regulate Blood-Brain-Barrier Permeability Induced by Acute Stress
Pamela Esposito, Nathan Chandler, Kristiana Kandere, Subimal Basu, Stanley Jacobson, Raymond Connolly, David Tutor and Theoharis C. Theoharides
"Stress activates the hypothalamic-pituitary-adrenal axis through release of corticotropin releasing hormone (CRH), leading to production of glucocorticoids that down-regulate immune responses.
Acute stress, however, also has proinflammatory effects that seem to be mediated through the activation of mast cells.
Stress and mast cells have been implicated in the pathophysiology of various inflammatory conditions, including some in the central nervous system, such as multiple sclerosis in which disruption of the blood-brain barrier (BBB) precedes clinical symptoms.
We previously showed that acute restraint stress increases rat BBB permeability to intravenous 99Tc gluceptate and that administration of the âmast cell stabilizerâ disodium cromoglycate (cromolyn) inhibits this effect. In this study, we show that the CRH-receptor antagonist Antalarmin blocks stress-induced 99Tc extravasation, whereas site-specific injection of CRH in the paraventricular nucleus (PVN) of the hypothalamus mimics acute stress.
This latter effect is blocked by pretreatment of the PVN with cromolyn; moreover, restraint stress cannot disrupt the BBB in the diencephalon and cerebellum of W/Wv mast cell-deficient mice.
These results demonstrate that CRH and mast cells are involved in regulating BBB permeability and, possibly, brain inflammatory disorders exacerbated by acute stress."
Mast Cells Migrate from Blood to Brain
Ann-Judith Silverman, Anne K. Sutherland, Marta Wilhelm and Rae Silver
Histamine in Migraine and Brain
Karl B. Alstadhaug MD, PhD
"There is substantial evidence that systemically given histamine may elicit, maintain, and aggravate headache.
The mechanisms for this are not known, and histamines do not penetrate the bloodâbrain barrier (BBB). However, circulating histamine may influence hypothalamic activity via the circumventricular organs that lack BBB.
In the rat, prolonged activation of meningeal nociceptors induced by dural mast cell degranulation has been observed.
Subcutaneous injections of Nâalphaâmethyl histamine, a catabolite of histamine with high affinity to the histamine H3 receptor, probably have some migraine preventive effect.
A negative feedback on histamine release from mast cells in proximity to Câfiber endings has been a postulated mechanism.
The involvement of mast cells has gained some attention over several decades, initially as a source of vasodilator substances19 and in view of migraine as an allergic disease,20-22 but later, more specific as an activator of a pain pathway underlying migraine headache.23
Neuronal histamine has gained rather scanty attention in migraine research, and with the growing knowledge of the central histaminergic system and indirect evidence for an important role of the hypothalamus in migraine pathophysiology, a review with future perspectives of the role of brain histamine is considered highly valuable."
https://headachejournal.onlinelibrary.wiley.com/doi/full/10.1111/head.12293
Here we go, spring training is coming soon, and as we all know, you canât tell whose the player without your score card. Thanks Jana!
Mast Cell Clonal Disorders: Classification, Diagnosis and Management
Merel C. OnnesLuciana K. TannoJoanne N. G. Oude Elberink
"Mast cell clonal disorders are characterized by the clonal proliferation of pathological mast cells as a result of somatic mutations in the KIT gene, most commonly the D816V mutation. Accumulation and degranulation of these cells causes a wide variety of symptoms.
Mast cell clonal disorders can be divided into mastocytosis and monoclonal mast cell activation syndrome, depending of the level of clonality. The severity of mastocytosis varies from an indolent variant with a good prognosis, to an aggressive condition with short life expectancy.
Diagnosis is based on demonstration of clonality and accumulation in the skin and in extracutaneous tissues. Treatment is highly individualized, and is based on the severity of the condition.
Treatment of patients with indolent systemic mastocytosis is aimed at reducing symptoms, using histamine H1 and H2 receptor antagonists as a starting point. In addition, associated conditions such as osteoporosis must be treated.
Treatment of advanced systemic mastocytosis is aimed at reducing mast cell load through cytoreductive therapy. The choice of such therapy depends on the KIT mutational status.
Though currently there is no curative treatment available, promising new therapies such as midostaurin are emerging that have demonstrated success in reducing symptoms and improving quality of life."
Inflammatory mediators and modulation of blood-brain barrier permeability.
Review article
Abbott NJ. Cell Mol Neurobiol. 2000.
"Histamine is one of the few central nervous system neurotransmitters found to cause consistent blood-brain barrier opening.
The earlier literature was unclear, but studies of pial vessels and cultured endothelium reveal increased permeability mediated by H2 receptors and elevation of [Ca2+]i and an H1 receptor-mediated reduction in permeability coupled to an elevation of cAMP. 9."
For Rhonda
Mast Cells and StressâA Psychoneuroimmunological Perspective
THEOHARIS C. THEOHARIDES, PHD, MD Tufts University School of Medicine, Boston, Massachusetts
H1R Antagonists for Brain Inflammation and Anxiety: Targeted Treatment for Autism Spectrum Disorders
"Hydroxyzine works through the mechanism of action as a potent H1 receptor (H1R) antagonist and serotonin reuptake inhibitor through a reduction of inflammation [39-41].
The reduction of H1R inhibits the production of proinflammatory cytokines [26] and brain mast cell activation [38-42], which induces a T-cell response that helps lower neuro inflammation.
This mechanism can provide relief from the more debilitating ASD symptoms like insomnia, uncontrolled behavior, communication issues, and locomotor activity [26].
This has been shown to help multiple sclerosis patients with similar symptoms by improving the neurological status of patients with Hydroxyzine [26].
This is a critical component because studies have demonstrated that the increase in serotonin (hyperserotonema) leads to a reduction in the activation of serotonin terminals [43]."
H1R Antagonists for Brain Inflammation and Anxiety: Targeted Treatment for Autism Spectrum Disorders
"Hydroxyzine works through the mechanism of action as a potent H1 receptor (H1R) antagonist and serotonin reuptake inhibitor through a reduction of inflammation [39-41].
The reduction of H1R inhibits the production of proinflammatory cytokines [26] and brain mast cell activation [38-42], which induces a T-cell response that helps lower neuro inflammation.
This mechanism can provide relief from the more debilitating ASD symptoms like insomnia, uncontrolled behavior, communication issues, and locomotor activity [26].
This has been shown to help multiple sclerosis patients with similar symptoms by improving the neurological status of patients with Hydroxyzine [26].
This is a critical component because studies have demonstrated that the increase in serotonin (hyperserotonema) leads to a reduction in the activation of serotonin terminals [43]."
Clinical Trial for Mast Cell Activation Syndrome patients!! In CHINA
Mmmmmmmmm Diphenhydramine â Breakfast of Champions!!!
Interesting comment in discussion by doctors in Tuesday PM TMS webinar on dosing, will have to verifyâŚ
Re: ER protocols⌠âyou run out of receptors past 100mg(??). Higher doses donât help, no place to parkâ. 400mg/day.
"A subsequent 1990 study found that the elimination half-life of diphenhydramine was 5.4 hours in children, 9.2 hours in young adults, and 13.5 hours in the elderly.[5 "
âOral bioavailability of diphenhydramine is in the range of 40% to 60%, and peak plasma concentration occurs about 2 to 3 hours after administration.[3] The primary route of metabolism is two successive demethylations of the tertiary amine. The resulting primary amine is further oxidized to the carboxylic acid.[3] The elimination half-life of diphenhydramine has not been fully elucidated, but appears to range between 2.4 and 9.3 hours in healthy adults.[4â
âMaximal effect is typically around two hours after a dose, and effects can last for up to seven hours.[7]â
"Adult
Acute Allergic Reactions
IV or IM: 10â50 mg; in a few patients, up to 100 mg may be required.
Alternatively, 25â50 mg recommended by some experts.(102 103)"
And all your tests results, at least one code between the 3 and 5 commercial, diagnosis, and successful resolution in one or 2 hour episode. (And no one ever looks like crap, needs a shave or hairbrush, has full makeup, has a NG tube actually sucking bile, tons of crap on the bedside table, and their arse hanging out of a torn raggedy old hospital gown)
Pollen Anatomy
Random Cool Flow for Anaphylaxsis in my Memory File Screen Saver. Anyone know where I stole this from???