Ureteral stones due to systemic mastocytosis: diagnostic and therapeutic characteristics.

Urolithiasis is expected to cause a considerable complication in patients with systemic mastocytosis. The aim of the present report is to demonstrate that due to pathological activation and irritability of mast cells, special features in the diagnostic investigation and therapy of urolithiasis have to be considered in patients with systemic mastocytosis. The clinical presentation, diagnostic investigation and therapeutic procedure of urolithiasis in a patient with systemic mastocytosis are described. Urolithiasis may be a significant complication of systemic mastocytosis. Non-contrast CT is the main tool for diagnosing urolithiasis after a detailed history and clinical exam. Patients with systemic mastocytosis should receive a premedication composed of a glucocorticoid and H(1)- and H(2)-histamine receptor antagonists. An increased vulnerability of mucosal tissues is expected in patients with systemic mastocytosis that may limit the options of operative and postoperative therapy. Opioids should be used cautiously for analgesia in patients with systemic mastocytosis.

Regulatory mechanisms underlying agmatine homeostasis in humans.

Regulation of agmatine homeostasis has so far only been poorly defined. In the present study, three mechanisms regulating human agmatine homeostasis were investigated. 1) Enzymatic regulation: expression of arginine decarboxylase, diamine oxidase, and ornithine decarboxylase in human colon neoplastic tissue was, at the mRNA level, about 75% and 50% lower and 150% higher, respectively, than in the adjacent normal tissue; expression of agmatinase was unchanged. 2) Bacteria-derived agmatine: ten representative bacteria strains of the human intestinal microbiota considerably differed in agmatine production and its efflux into their surrounding fluid, suggesting that the composition of the intestinal microbiota influences the agmatine availability in the gut lumen for absorption. 3) Regulation of blood plasma agmatine concentration by the human liver: at low concentrations in portal venous blood plasma, agmatine either slightly increased or further decreased in blood plasma through liver passage. Above a threshold of 14 ng/ml agmatine in the portal venous blood plasma, substantial hepatic agmatine removal from blood occurred. Taken together, a perturbation of agmatine homeostasis has been proven to be involved in the regulation of malignant cell proliferation. The amount of agmatine available for absorption, which is an important physiological source of agmatine in the human organism, should differ considerably depending on the composition of the bacterial flora in the chyme since the various species of intestinal bacteria largely differ in their ability to form agmatine. Finally, evidence has been presented that the liver plays a crucial physiological role in the maintenance of agmatine homeostasis in the human organism.

Intestinal tumor and agmatine (decarboxylated arginine): low content in colon carcinoma tissue specimens and inhibitory effect on tumor cell proliferation in vitro.

BACKGROUND: The polyamine system is a promising target for anticancer therapy. Ideally, an antineoplastic compound affecting this system should inhibit both ornithine decarboxylase and the polyamine transporter, and toxicity should be mild. Agmatine, decarboxylated L-arginine, appears to be such a compound. METHODS: Adenosine triphosphate levels and the protein content of cell populations in culture were identified as surrogate markers for cell count. Agmatine content in cells and tissue specimens was measured by high-performance liquid chromatography. Antizyme levels were estimated by Western blotting. RESULTS: Agmatine inhibited the proliferation of six human intestinal tumor cell lines in a concentration-dependent manner; this inhibition probably was attributable to an interaction between agmatine and the intracellular polyamine system. Consistent with the inverse relation between cell proliferation and agmatine concentration was the finding that agmatine content in human colon carcinoma tissue was approximately one-half as great as it was in adjacent macroscopically normal tissue. CONCLUSIONS: The results of the current study were compatible with the hypothesis that agmatine possesses antineoplastic action against intestinal tumor cells. It is likely that this activity is attributable to agmatine's regulatory role in polyamine homeostasis.