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Abstract Mast cell activation disease comprises disorders characterized by accumulation of genetically altered mast cells and/or abnormal release of these cells' mediators, affecting functions in potentially every organ system, often without causing abnormalities in routine laboratory or radiologic testing. In most cases of mast cell activation disease, diagnosis is possible by relatively non-invasive investigation. Effective therapy often consists simply of antihistamines and mast cell membrane-stabilising compounds supplemented with medications targeted at specific symptoms and complications. Mast cell activation disease is now appreciated to likely be considerably prevalent and thus should be considered routinely in the differential diagnosis of patients with chronic multisystem polymorbidity or patients in whom a definitively diagnosed major illness does not well account for the entirety of the patient's presentation.

Objective. Sequencing efforts to discover mutations in the tyrosine kinase Kit related to systemic mast cell disorders have so far been focused mainly on only a few of the 21 exons of the encoding gene c-kit, thus considerably limiting the possibility to quantitatively reveal pathogenetic relationships. The purpose of this study was to analyze and compare the total sequence of Kit tyrosine kinase at the level of the mRNAs obtained from patients with clear systemic signs of a pathologically increased mast cell mediator release and those from healthy volunteers. Material and methods. Kit encoding mRNA isolated from mast cell progenitors in peripheral blood from 17 patients with a mast cell activation disorder and from 5 healthy volunteers as well as from the human mast cell leukemia cell line HMC1 was analyzed for alterations. Results. Multiple novel point mutations and six isoforms of Kit which are due to alternative mRNA splicing were detected. One isoform, the insertion of a glutamine residue at amino acid position 252, was found to be a new splice variant expressed in all patients but in none of the healthy volunteers. Conclusions. Systemic mast cell activation disorder was pathogenetically characterized by two or more alterations in the Kit tyrosine kinase providing not only a means of confirming the diagnosis, but also of assessing prognosis and of starting adequate therapeutic interventions. The insertion of Q252 appears to be pathognomic for that disease, providing a novel means for the identification of chronic non-specific gastrointestinal symptoms as manifestations of a systemic mast cell activation disorder. [ABSTRACT FROM AUTHOR]

The authors report on (1) the absorption of agmatine from the gastrointestinal tract as an important source of this polycation in the organism, (2) its organ distribution, and (3) its putative role in liver regeneration. When rats received 0.5 mCi [14-C]agmatine contained in 5 grams of standard rat chow after a fasting period of 24 hours, radioactivity was recovered in all organs investigated, in blood, and in urine. In the liver 67% ± 7% of administered radioactivity was found. After partial (two-thirds) hepatectomy, administration of 250 mg and 500 mg agmatine by gavage for 6 days reduced liver regeneration at day 7 by 20% and 22%, respectively, compared with animals that received no agmatine. Agmatine is absorbed from the gastrointestinal tract, probably by means of a specific transporter. It is likely that agmatine in the chyme of the gut represents an essential source of agmatine in the tissues of the organism. An increase in the availability of gastrointestinal agmatine for absorption impairs liver regeneration and may contribute to the development of liver diseases. [ABSTRACT FROM AUTHOR]