Bradykinin theory and Vitamin D.
Makes sense to me, fits data. Be interested in cohort testing results.
Histamine is a major mediator of inflammation, anaphylaxis, and gastric acid secretion; in addition, histamine plays a role in neurotransmission. Our understanding of the physiological and pathophysiological roles of histamine has been enhanced by the development of subtype-specific receptor antagonists and by the cloning of 4 receptors for histamine. Competitive antagonists of H1 receptors are used therapeutically in treating allergies, urticaria, anaphylactic reactions, nausea, motion sickness, insomnia, and some symptoms of asthma. Antagonists of the H2 receptor are effective in reducing gastric acid secretion. The peptide, bradykinin, has cardiovascular effects similar to those of histamine and plays prominent roles in inflammation and nociception.
Basic polypeptides often are effective histamine releasers, and over a limited range, their potency generally increases with the number of basic groups. For example, bradykinin is a poor histamine releaser, whereas kallidin (Lys-bradykinin) and substance P, with more positively charged amino acids, are more active. Some venoms, such as that of the wasp, contain potent histamine-releasing peptides. Basic polypeptides released upon tissue injury constitute pathophysiological stimuli to secretion for mast cells and basophils.
Determination of Plasma Heparin Level Improves Identification of Systemic Mast Cell Activation Disease
Milda Vysniauskaite, Hans-Jörg Hertfelder, […], and Gerhard J. Molderings
PLoS One. 2015; 10(4): e0124912.
Since only a few MC mediators are currently established as biomarkers of MCAD, the sensitivity of plasma heparin level (pHL) as an indicator of increased MC activation was compared with that of serum tryptase, chromogranin A and urinary N-methylhistamine levels in 257 MCAD patients. Basal pHL had a sensitivity of 41% in MCAS patients and 27% in SM patients.
Non-pharmacologic stimulation of MC degranulation by obstruction of venous flow for 10 minutes increased the sensitivity of pHL in MCAS patients to 59% and in SM patients to 47%. In MCAS patients tryptase, chromogranin A, and N-methylhistamine levels exhibited low sensitivities (10%, 12%, and 22%, respectively), whereas sensitivities for SM were higher (73%, 63%, and 43%, respectively).
Taken together, these data suggest pHL appears more sensitive than the other mediators for detecting systemic MC activity in patients with MCAS.
The simple, brief venous occlusion test appears to be a useful indicator of the presence of pathologically irritable MCs, at least in the obstructed compartment of the body.
Mast-cell heparin demystified
James L. Zehnder &
Stephen J. Galli
Nature volume 400, pages714–715
The functions of heparin stored in resting mast cells and that released into the tissues by activated mast cells are probably distinct.
However, given that the consequences of mast-cell activation examined by Humphries et al.4 and Forsberg et al.5 — enhanced vascular permeability and recruitment of white blood cells (leukocytes) — were not substantially influenced by heparin, which mast-cell functions might be?
First, activation of mast cells has been shown to lead to clotting in the adjacent connective tissue, where mast cells normally mature15 (Fig. 1b). Perhaps such clotting is enhanced in the NDST-2-deficient mice.
Second, as well as being an anti-coagulant, heparin can bind certain cytokines, chemokines and growth factors, many of which are produced by mast cells6,7,16.
Finally, depending on the circumstances, heparin can either promote or suppress the proliferation and migration of cells involved in vascular development, atherosclerosis, wound healing and tissue remodelling2.
Heparin also regulates the distribution and enzymatic activity of certain mast-cell proteases7,17
Characterization of Mast Cell Activation Syndrome
Lawrence B. Afrin, M.D., Sally Self, M.D., […], and John Lazarchick, M.D.
Am J Med Sci. 2017 Mar; 353(3): 207–215.
The relative utilities of various MC mediators tested in diagnostic assessments for MCAS were found in this study (at one institution) to be similar to another large cohort (at a separate institution) recently reported. 
The present study provides further evidence that plasma heparin is the most useful marker of MC activation, followed closely by prostaglandin D2 and chromogranin A.
Chromogranin A levels, though, can be confounded by heart or renal failure, proton pump inhibitor use, or neuroendocrine cancer. Also, other work has clarified the importance of continuous specimen chilling, including use of refrigerated centrifugation for plasma separation, when seeking plasma heparin levels. 
Furthermore, our present study adds to evidence mounting in the last decade that the serum tryptase level – while still quite useful as an initial laboratory screen for MC neoplasia in mastocytosis – is a relatively poor indicator of MC activation, and old precepts that MC disease is unlikely when the serum tryptase level is normal can no longer stand.
It is clear that mastocytosis is less likely when the serum tryptase level is below the threshold of 20 ng/ml defined in the World Health Organization diagnostic criteria for SM (one study found 30% of indolent SM patients had serum tryptase levels < 20 ng/ml ), but there is at least some elevation in tryptase in virtually all SM patients (96% ). In contrast, only 62 (16%) of the 388 MCAS patients in this study tested at least once for a serum tryptase level were found to have any elevation in this parameter, and only 15 (24%) of these 62 (or 3.9% of the overall population tested at least once for tryptase) showed at least one serum tryptase level > 20 ng/ml.
Tryptase was tested more than once in 88 patients, but in only 2 patients was the tryptase level found > 20 ng/ml more than once.
Clearly, serum tryptase at a normal level, or elevated to < 20 ng/ml or perhaps even somewhat above this level, is insufficient to exclude MCAS. A rise in serum tryptase (over the level determined at an “asymptomatic” baseline, which may not exist) of 20% + 2 ng/ml has been proposed as a discriminator for MCAS , but no data supporting this proposal have been published.
The big question is, with three more days of torrential hurricane rains and tropical cyclone winds, how do I stretch my Sally Snacks?
Pancreatic and pulmonary mast cells activation during experimental acute pancreatitis
Inmaculada Lopez-Font, Sabrina Gea-Sorlí, […], and Daniel Closa
World J Gastroenterol. 2010 Jul 21; 16(27): 3411–3417.
Pancreatic mast cells play an important role in triggering the local and systemic inflammatory response in the early stages of acute pancreatitis. In contrast, lung mast cells are not directly involved in the systemic inflammatory response related to pancreatic damage.
Acute pancreatitis represents a substantial clinical problem with increasing incidence and it is associated with high morbidity and mortality. The most important predictor of mortality is the development of persistent or multiple organ failure and the commonest affected organ is the lung[2,3]. In these cases, acute lung injury is frequently related to early deaths in the first week of the disease.
The mechanisms involved in triggering distant organ inflammation are unclear, however, in addition to the release of activated hydrolytic enzymes, different pathways have been reported, including cytokines, oxygen-derived free radicals or activated complement.
Among these mechanisms, mast cells have been reported to contribute to several aspects of pancreatitis-associated lung injury. These cells release a number of mediators, including histamine, tumor necrosis factor (TNF)α or monocyte chemotactic protein-1 (MCP-1) which could have a strong effect on pulmonary endothelial cells, thus potentiating the progression of inflammation[8,9].
The expression of different adhesion molecules increases early after pancreatitis induction, and in some of these molecules this increase could be prevented by administering mast cell degranulation inhibitors such as sodium cromolyn[10,11].
These observations suggest that masts cells are responding to mediators released during pancreatitis and, when activated, play a role in the induction of endothelial lung dysfunction and in the progression of the local and systemic inflammatory process.
Pancreatitis; not always about alcohol or gallstones
2nd International Conference on Internal Medicine & Hospital Medicine
September 13-14, 2017 Dallas, USA
A commonly diagnosed condition such as Pancreatitis with well-known causes becomes a diagnostic challenge when no clear etiology can be determined.
The following case explores the possible link between Mast Cell Activation Disorder/ Syndrome (MCAS) and pancreatitis.
A 35 year old female who carries the rare diagnosis of MCAS was presented for an elective ventral hernia repair. The surgery itself was uneventful, however on POD 1 patient developed sudden onset of severe epigastric abdominal pain. CT abdomen was obtained with findings suspicious for possible pancreatitis. The CT findings prompted a check of this patient’s lipase. Lipase was found to be markedly elevated at 4674.
Common causes of pancreatitis such as gallstones, alcohol and medication-induced were explored but the etiology was unable to be determined. Keeping this patient’s unique background history in mind, the pancreatitis was attributed to her MCAS.
Patient was treated with IVF and bowel rest and fortunately recovered from her acute bout of pancreatitis rather quickly.
First described in 1991 but not termed until the late 2000’s ‘mast cell activation syndrome’ is a collection of illnesses precipitated by mast cells (MC) which inappropriately activate inflammatory mediators.
The illness is systemic and can affect almost any organ including the pancreas.
Patients afflicted by this mysterious condition experience episodes labeled mast cell flare ups. The presentation of a flare can mimic symptoms of anaphylaxis in some cases.
The precipitating factors are numerous but can be as simple as the application of a topical substance such as lotion or perfume.
The treatment of this rare disorder is still being studied however current therapy is aimed at controlling and ameliorating the disease by inhibiting the release and blocking the effects of the released mediators by MC. Trigger avoidance also plays a key role.
The diagnosis of MCAS involves is suspected with a rise in tryptase levels. Tryptase is the most abundant mediator store in Mast cells. Bone marrow aspiration may reveal MC abnormalities like spindling and small clustering of two or three cells.
Over the course of understanding MC mediators, we now acknowledge their involvement in maintaining homeostasis of many body’s tissues and organ systems. Hence it’s not surprising to learn these mediators can have an effect not just at a cellular level but at a clinical level too. In this case the inflammation of the pancreas could be explained by MCAS.
In more recent years the link between activation of mast cells and the development of acute pancreatitis has been appreciated.
One study suggests that release of MC mediators pose inflammation and enzymatic assault to the organ. Increased circulating histamine levels have also been associated which worsens organ injury more so if derived from pancreatic MC.
Receptors trigger the release of mediator either piece meal, or explosively degranulating as shown here.
Why yes, we’re having a wonderful time, just a little shower and wind.
14 inches or rain so far overnight, and from 12 to 20 more to come.
Hurricane Ivan sequel, 16 years to the day.
If you have been diagnosed with osteopenia, would you mind sharing your mast cell related diagnosis with me? I was recently diagnosed with widespread osteopenia, which I understand is comorbid with mast cell disorders.
Does anyone take a DAO supplement or some sort of organ (like liver) supplement? I am new to MCAS and trying to figure out what my body needs.
What about food? What is the #1 food you avoid? And what are your favorite low-histamine foods do you eat?
I often use this website to look at the inactive ingredients for all my meds, particularly when the supplier to the pharmacy periodically changes.
Prostaglandins and flushing
The prostaglandins are a group of lipids made at sites of tissue damage or infection that are involved in dealing with injury and illness. They control processes such as inflammation, blood flow, the formation of blood clots and the induction of labour.
Alternative names for prostaglandins
Prostaglandin D2; prostaglandin E2; prostaglandin F2; prostaglandin I2 (which is also known as prostacyclin); a closely related lipid called thromboxane
What are prostaglandins?
Anti-inflammatory drugs, such as aspirin and ibuprofen, work by blocking the action of the cyclooxygenase enzymes and so reduce prostaglandin levels. This is how these drugs work to relieve the symptoms of inflammation. Aspirin also blocks the production of thromboxane and so can be used to prevent unwanted blood clotting in patients with heart disease.
Mechanism of action of the drug aspirin. Aspirin works by stopping prostaglandin being made: aspirin molecules (blue hexagons) enter the cell and chemically modify the cyclooxygenase enzyme (purple) to prevent prostaglandin being made.
Supplement-drug interactions that physicians should know about
A supplement-drug interaction occurs when a supplement competes with a drug for the same mechanism of absorption, distribution, metabolism, or excretion (ADME).
If the supplement elbows out the prescription medication, it can lead to a different concentration of the drug at the site of action. So, the drug may not work as intended or result in unexpected adverse effects.
More than 1,000 enzymes are involved in ADME mechanisms, and they’re categorized into four basic families:
CYP - cytochrome P450 (CYP) drug metabolism enzymes
UGT - uridine diphosphate-glucuronosyltransferase (UGT) conjugating enzymes
ABC - adenosine triphosphate-binding cassette (ABC) drug uptake/efflux transporters
OATP - organic anion-transporting polypeptide (OATP) drug transporters
Importantly, six CYP enzymes (CYP1A2, CYP2C9, CYP2C19, CYP2D6, CYP2E1, CYP3A4) metabolize nearly 80% of all prescribed drugs.
Other important ADME enzymes in supplement-drug interactions are OATP1A1, OATP1A2, OATP2B1, and the ABC transporter P-glycoprotein (P-gp).