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PubMed2002

Expression of diamine oxidase (histaminase) in guinea-pig tissues.

The expression of mRNA for diamine oxidase (histaminase) and the enzyme activity in guinea-pig tissues were investigated. Reverse transcription-polymerase chain reaction analysis revealed that the message corresponding to the long form present in humans and rats was expressed abundantly in the small intestine and liver. Small but detectable amounts of diamine oxidase mRNA were observed in the kidney, stomach, cerebellum, thalamus+hypothalamus, and cerebral cortex. Northern blot analysis showed that the message (2.8 kb in size) was observed abundantly in the liver and small intestine and was detectable in the kidney and stomach but not in the brain or lung. In situ hybridization showed that diamine oxidase mRNA was localized throughout the liver and epithelial cells of the small intestine. Diamine oxidase activity was detected at various levels in different tissues of the guinea-pig at the following relative abundance: liver>small intestine>lung, kidney>stomach. Histamine dose-dependently induced the contraction of sections of the guinea-pig small intestine, and the pretreatment of the tissue section with aminoguanidine (100 microM), a diamine oxidase inhibitor, but not with S-[4-(N,N-dimethylamino)butyl]isothiourea (100 microM), an inhibitor of histamine N-methyltransferase, shifted the dose-response curve of histamine-induced contraction to lower concentrations. These results suggest that diamine oxidase has a crucial role in the degradation of histamine in the guinea-pig small intestine and probably in the liver.

Amine Oxidase (Copper-Containing)↗

PubMed1980

Diamine oxidase (histaminase). A circulating marker for rat intestinal mucosal maturation and integrity.

Diamine oxidase (histaminase) is an enzyme found in high concentrations in the intestinal mucosa of humans and other mammalian species. We investigated whether plasma and mucosal levels of diamine oxidase activity reflect both the maturational status of the mucosa during its development in the newborn rate and the degree of mucosal damage during its injury in the adult rat. Litter mates were reared under identical conditions and killed at different ages from day 0 to day 40 after birth. Diamine oxidase in the small intestine was low at birth, increased gradually with age, reached a peak at 22 d, and then remained at normal adult levels, similar to the developmental patterns of maltase and sucrase. Plasma diamine oxidase rose in parallel with intestinal levels (n = 500, r = 0.84, P less than 0.001), reached a peak at 24 d, and then remained at normal adult levels. Diamine oxidase activity in 15 nonintestinal tissues was less than 5% of ileal mucosal activity, and no nonintestinal activities showed increase with age. Adult rat intestinal loops were perfused with hyperosmolar sodium sulfate solutions to produce selective damage to villus mucosa. With increasing mucosal damage, there was a progressive decrease in the enzyme activities studied; first, lactase levels fell, then maltase and sucrase, and finally mucosal and plasma diamine oxidase activity levels fell. The decrease in plasma diamine oxidase reflected the degree of mucosal damage (n = 29, P less than 0.04). Diamine oxidase activity is thus unique among intestinal mucosal enzymes studied to date in that circulating levels can serve as a marker of mucosal maturation and integrity.

Amine Oxidase (Copper-Containing)↗

PubMed1982

The prognostic and biological significance of cellular heterogeneity in medullary thyroid carcinoma: a study of calcitonin, L-dopa decarboxylase, and histaminase.

We evaluated the cellular distribution of calcitonin (CT), L-dopa decarboxylase (DDC), and histaminase [diamine oxidase (DAO)] in 33 patients with medullary thyroid carcinoma (MTC). CT immunostaining was uniform (greater than 90% of the cells) and intense (4+) in lesions from 7 patients with C-cell hyperplasia and 6 with microscopic MTC: conversely, patchy CT staining (less than 40% of the cells) and diminished intensity (1+) were found in metastases from 8 patients who died of virulent disease. In 17 patients who underwent thyroidectomy for macroscopic cervical MTC with no evidence distant metastases, CT staining was intense (3-4+) and homogeneous (greater than 90%) in 11 subjects who were well 0.5-16 yr postoperatively. Six patients with similar clinical presentations had heterogeneous staining for CT in primary tumor (less than 40% of the cells; 1-2+ intensity); 5 died of disseminated MTC 0.5-5 yr postoperatively (P less than 0.001). Biochemical studies of distant metastases revealed an inverse relationship between the distribution of CT and that of both relationship between the distribution of CT and that of both DDC (r = 0.71; P less than 0.01) and DAO (r = 0.81; P less than 0.001). We conclude that cellular heterogeneity in MTC tissue is associated with a distinct biochemical pattern, and its presence, whether in a primary or metastatic lesion, indicates a virulent neoplasm associated with a grave prognosis.

Adult↗

PubMed1978

[Changes in the histamine concentration, histaminase activity and histaminopexic index of the blood in acute cerebral circulatory disorders].

In 67 patients with ischemic and hemorrhagic strokes the authors studied the histamine metabolism in its development correlating the observed changes (in the acute stage of the disease and following medicative therapy). The results demonstrated that in the acute period of the disease the histamine content in the blood increases, while the histaminase activity and the histaminpexic index decreases. It was shown that these changes are more distinct in hemorrhagic strokes. In extensive processes involving the subcortical nodes, the internal capsule and hypothalamus, these parameters show deeper changes and in the future do not normalize. Such studies may be of topico-diagnostic importance as well as of prognostic and therapeutical significance.

Acute Disease↗

PubMed1988

[Function of the histamine-histaminase system in the dynamics of experimental acute pancreatitis].

The action of histamine-histaminase in progressing pancreatitis has been studied in conformity with neurohumoral theory of pancreatitis pathogenesis. Phase modifications have been revealed. Violation of the relations arising in the system during the first 24 hours of the disease is brought to normal in the subsequent period of pathological process. The study of the system makes it possible to agree with the recommendation of the use of antihistamine preparations in the clinical practice.

Acute Disease↗

PubMed1987

Circadian variations of the absolute eosinophil count and serum histaminase activity in tropical pulmonary eosinophilia.

Nine healthy volunteers and 25 tropical pulmonary eosinophilia (TPE) patients were used to study circadian variations of absolute eosinophil count (AEC) and serum histaminase activity (SHA). A marked circadian variation was found in AEC for healthy volunteers and TPE patients with the worst symptoms in the late evening and morning hours only; no rhythm could be detected in SHA for healthy subjects. However, TPE patients with worst symptoms in the late evening hours did exhibit a significant rhythm in SHA. Increased SHA in all TPE patients at all time-points of the 24 hour day-night cycle, irrespective of the worsening hours of symptoms in comparison to healthy controls, could be due to increased histamine production in such situations.

Amine Oxidase (Copper-Containing)↗

PubMed1978

[Possible clinical importance of the activation of diamine oxidase (histaminase) in heparin treatment of renal diseases (author's transl)].

Heparin up until now has been in renal diseases for its anticlotting effect. An additional property of heparin is the activation of the diamine oxidase (histaminase). Whether a possible clinical importance of the diamine oxidase activation in heparin treatment of renal diseases exists or not remains unknown and is discussed.

Amine Oxidase (Copper-Containing)↗

PubMed1976

Serum level changes of endogenous and postheparin diamine oxidase (histaminase) in clinical and experimental hepatitis.

In patients suffering from acute viral hepatitis (n = 12) an about 50 per cent decrease of serum diamine oxidase (DAO, histaminase, E.C.N. 1.4.3.6) was detected as compared to a healthy control group (n = 24). Normally, the intravenous injection of heparin is promptly followed by a marked rise of plasma DAO. In viral hepatitis, however, after application of heparin (200 IU/kg b.w., i.v.) the enzyme release from the visceral organs into the plasma was markedly decreased. There was an inverse correlation between the serum glutamic pyruvic transaminase (SGPT) and the postheparin enzyme. Normalization of SGPT occurred before the normalization of post-heparin diamine oxidase (PHD). In galactosamine "hepatitis" of rats (800 mg Gal-N/kg b.w., i.p.), in contrary to human viral hepatitis plasma DAO increased about 5-fold after heparin application. This increased PHD in plasma of Gal-N rats was correlated to enhanced animal's endogenous plasma DAO activity (r=0.685, p less then 0.0005, n = 54). The cause of these enzyme activity changes and its possible pathophysiological meaning are still unknown. It is concluded from these experiments that in Gal-N "hepatitis" of rats plasmatic DAO level changes are mediated by endogenous heparin, released from disrupted mast cells. Increased basal DAO levels correspond to the enhanced release after heparin application, both possibly induced by less stable binding of the enzyme to the cells of the small intestine in inflammation. Both, decreased endogenous and post-heparin DAO levels in human hepatitis would correspond to a depletion of the enzyme containing organs.

Acute Disease↗

PubMed1976

Diamine oxidase (histaminase) in chronic renal disease and its inhibition in vitro by methylguanidine.

The activity of plasma diamine oxidase (pyridoxal containing amine oxidase, histaminase, DAO), E. C. N. 1. 4. 3. 6., was found to be normal in 14 patients with chronic renal disease of different origins. However, after administration of heparin (200 IU/kg body weight, i.v.), the release of the enzyme into the plasma of the patients was markedly decreased when compared to that found in a group of 8 healthy volunteers. In patients with chronic renal failure the plasma concentration of pyridoxalphosphate, the coenzyme of DAO, was found to be significantly decreased. Furthermore methylguanidine, which is thought to be an important uremic toxin, was shown to be a potent non-competitive inhibitor of DAO in vitro (Ki5 X 10(5) M). The organ concentrations of methylguanidine are thought to correspond with the Ki value detected, as distribution studies using the tritiated toxin revealed organ accumulation up to five times the plasma level. Therefore, the decrease of DAO release after heparin stimulation in patients with chronic renal failure may be explained, in part, by inhibition of the enzyme as well as by a decreased coenzyme level. The results suggest that disturbed histamine metabolism may be involved in the production of some of the clinical symptoms commonly associated with chronic renal failure.

Adolescent↗

PubMed1964