More Poopology. We bring you the straight…well…stuff
WHY MAST It Be So Hard? MAST CELL DISORDERS OF THE GI TRACT Scott Owens, M.D. Leslie Aldrich, M.D. 05/19/19
Mast Cells in Gastrointestinal Disease
David B. Ramsay, MD, Sindu Stephen, MD, […], and David B. Doman, MD, FACP, FACG
GI and Mast Cell Issues
Note: Years of debilitating migraines mostly disappeared once I began my Masto. medicine regimen including oral cromlyn…
PACAP and its receptors in cranial arteries and mast cells
Inger Jansen-Olesen and Sara Hougaard Pedersen
Dr Theoharides was right back in 2004.!
The role of mast cells in migraine pathophysiology
Theoharis C. Theoharides*, Jill Donelan, Kristiana Kandere-Grzybowska1, Aphrodite Konstantinidou
"Migraines are episodic, typically unilateral, throbbing headaches that occur more frequently in patients with allergy and asthma implying involvement of meningeal and/or brain mast cells.
These mast cells are located perivascularly, in close association with neurons especially in the dura, where they can be activated following trigeminal nerve, as well as cervical or sphenopalatine ganglion stimulation.
Neuropeptides such as calcitonin gene-related peptide (CGRP), hemokinin A, neurotensin (NT), pituitary adenylate cyclase activating peptide (PACAP), and substance P (SP) activate mast cells leading to secretion of vasoactive, proinflammatory, and neurosensitizing mediators, thereby contributing to migraine pathogenesis.
Brain mast cells can also secrete proinflammatory and vasodilatory molecules such as interleukin-6 (IL-6) and vascular endothelial growth factor (VEGF), selectively in response to corticotropin-releasing hormone (CRH), a mediator of stress which is known to precipitate or exacerbate migraines.
A better understanding of brain mast cell activation in migraines would be useful and could lead to several points of prophylactic intervention."
Dr Theoharides was right back in 2004.!
The role of mast cells in migraine pathophysiology
Theoharis C. Theoharides*, Jill Donelan, Kristiana Kandere-Grzybowska1, Aphrodite Konstantinidou
"Migraines are episodic, typically unilateral, throbbing headaches that occur more frequently in patients with allergy and asthma implying involvement of meningeal and/or brain mast cells.
These mast cells are located perivascularly, in close association with neurons especially in the dura, where they can be activated following trigeminal nerve, as well as cervical or sphenopalatine ganglion stimulation.
Neuropeptides such as calcitonin gene-related peptide (CGRP), hemokinin A, neurotensin (NT), pituitary adenylate cyclase activating peptide (PACAP), and substance P (SP) activate mast cells leading to secretion of vasoactive, proinflammatory, and neurosensitizing mediators, thereby contributing to migraine pathogenesis.
Brain mast cells can also secrete proinflammatory and vasodilatory molecules such as interleukin-6 (IL-6) and vascular endothelial growth factor (VEGF), selectively in response to corticotropin-releasing hormone (CRH), a mediator of stress which is known to precipitate or exacerbate migraines.
A better understanding of brain mast cell activation in migraines would be useful and could lead to several points of prophylactic intervention."
"Dural mast cell degranulation clearly represents a relevant mechanism that might lead to activation and sensitization of the trigeminovascular pain pathway.
Upon activation, mast cells are known to degranulate and release a host of inflammatory mediators. Exogenous migraine triggers, CGRP, NTG and PACAP, can cause dural mast cell degranulation [18, 110, 116], and subsequent release of inflammatory mediators.
Furthermore, specific dural mast cell degranulation produces a long-lasting sensitization of trigeminal primary afferent neurons [88, 156], suggesting this neuro-inflammatory mechanism may be directly involved in mediating the underlying neurophysiological changes that results in primary headache, particularly in migraine."
Shared Fate of Meningeal Mast Cells and Sensory Neurons in Migraine
Duygu Koyuncu Irmak, Erkan Kilinc, and Fatma Tore
"Mast cell-sensory nerve relationship in migraine pathophysiology is versatile and not fully mapped, yet.
The main difficulty in understanding these complex interactions that constitute the bi-directional cross-talk of the mast cells, nerves and the vessel components comes from multi-dimensional channels of communication working in harmony or disharmony.
The diverse interpretation of the messages that are released from dose-dependent ligand response constitutes a wide spectrum of commentary remarks.
Thus, the clinical evidence suggests that there is no one-fit-all treatment choice for migraine.
In order to investigate the effective and safe treatment options which entail the combination of the existing monoclonal antibodies and mast cell stabilizers and triptans for the proper combat with the least side effects and the most efficacious cure methods could be evaluated."
Baltimore Area Support Group on Saturday!! Topic: Favorite Mast Cell Disease resources (FB groups, books, blogs, websites, etc.)
RSVP to MastCellKell@protonmail.com
I’ve had to do this with my prior Cardiologists, Pulmonologist, and GI docs and one Allergist. Couldn’t handle complex multiple system interactions, wouldn’t timely respond, wouldn’t coordinate with other doctors. Sadly, while the doctors weren’t up to snuff, some of their PAs were great, and I miss them.
Tonight 700 to 830 pm CST for TMS Members who have registered.
We are very excited about our first TMS Patient Voice Forum-MCAS this Tuesday February 11, 2020 at 8-9:30 PM Eastern Time in recognition of Rare Disease Month. Panelists include Mariana Castells, MD, PhD; Matthew Hamilton, MD; Marla Barkov, MD; Charity Fox, MD; and Theoharis Theoharides, MD, PhD. TMS members were invited to resubmit questions or comments to be considered for the forum. Anyone in the mast cell community can register in advance and participate by listening into the Zoom webinar. If you would like to participate more fully for future webinars on Mastocytosis, Advanced Variants of Mastocytosis, Hereditary alpha Tryptasemia, and Pediatric Mast Cell Disease by being able to resubmit questions, all you need to do is join TMS, and it is free! Please go to our our website:
Please note that we are no longer accepting questions for this MCAS forum as we have already had a terrific response. We will need to schedule a second MCAS forum to accommodate them, so please check our website for details.
Brain Fog…Eat celery in the morning??
Brain “fog,” inflammation and obesity: key aspects of neuropsychiatric disorders improved by luteolin Theoharis C. Theoharides1,2,3,4*, Julia M. Stewart1, Erifili Hatziagelaki5 and Gerasimos Kolaitis
"Brain “fog” may be due to inflammatory molecules, including adipocytokines and histamine released from mast cells (MCs) further stimulating microglia activation, and causing focal brain inflammation.
Recent reviews have described the potential use of natural flavonoids for the treatment of neuropsychiatric and neurodegenerative diseases.
The flavone luteolin has numerous useful actions that include: anti-oxidant, anti-inflammatory, microglia inhibition, neuroprotection, and memory increase. A liposomal luteolin formulation in olive fruit extract improved attention in children with ASDs and brain “fog” in mastocytosis patients.
Methylated luteolin analogs with increased activity and better bioavailability could be developed into effective treatments for neuropsychiatric disorders and brain “fog.”"
Happy Birthday to Dr Theoharides!
