Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0016382 (flushing)
 6,387 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Nicotinic acid (niacin) is a B vitamin which is also a potent hypolipidemic agent. However, intense flushing occurs following ingestion of pharmacologic doses of niacin which greatly limits its usefulness in treating hyperlipidemias. Previous studies have demonstrated that niacin-induced flushing can be substantially attenuated by pre-treatment with cyclooxygenase inhibitors, suggesting that the vasodilation is mediated by a prostaglandin. However, the prostaglandin that presumably mediates the flush has not been conclusively determined. In this study we report the finding that ingestion of niacin evokes the release of markedly increased quantities of PGD2 in vivo in humans. PGD2 release was assessed by quantification of the PGD2 metabolite, 9 alpha, 11 beta-PGF2, in plasma by gas chromatography mass spectrometry. Following ingestion of 500 mg of niacin in three normal volunteers, intense flushing occurred and plasma levels of 9 alpha, 11 beta-PGF2 were found to increase dramatically by 800, 430, and 535-fold. Levels of 9 alpha, 11 beta-PGF2 reached a maximum between 12 and 45 min. after ingesting niacin and subsequently declined to near normal levels by 2-4 hours. Levels of 9 alpha, 11 beta-PGF2 in plasma correlated with the intensity and duration of flushing that occurred in the 3 volunteers. Release of PGD2 was not accompanied by a release of histamine which was assessed by quantification of plasma levels of the histamine metabolite, N tau-methylhistamine. This suggests that the origin of the PGD2 release is not the mast cell. Only a modest increase (approximately 2-fold) in the urinary excretion of the prostacyclin metabolite, 2,3-dinor-6-keto-PGF1 alpha, occurred following ingestion of niacin and no increase in the excretion of the major urinary metabolite of PGE2 was found. These results indicate that the major vasodilatory PG released following ingestion of niacin is PGD2. The fact that markedly increased quantities of PGD2 are released suggests that PGD2 is the mediator of niacin-induced vasodilation in humans.
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PMID:Release of markedly increased quantities of prostaglandin D2 in vivo in humans following the administration of nicotinic acid. 247 89

Plasma levels of histamine and Nt-methylhistamine were measured simultaneously by high performance liquid chromatography during the intravenous infusion of histamine acid phosphate in six normal volunteers. Progressive, dose-related increases in plasma histamine were noted, reaching a maximum value of 3.1 +/- 0.14 ng ml-1 corresponding to a maximum infusion rate of 180 ng kg-1 min-1 (means +/- SEM). Increases in plasma histamine were accompanied by a significant dose-related fall in mean diastolic blood pressure (baseline 74.0 +/- 4.4 mm Hg falling to 60.0 +/- 3.3 mm Hg at maximum infusion rate, p less than 0.001) and an increase in pulse rate (baseline 76.3 +/- 2.8 beats min-1 rising to 89.24 beats min-1 at maximum infusion rate, p less than 0.05). All subjects exhibited facial flushing, the threshold plasma histamine level for this effect being 1.3 +/- 0.15 ng ml-1 corresponding to an infusion rate of 60 ng kg-1 min-1. Elevation of plasma Nt-methylhistamine was seen in only one subject, who exhibited a level of 0.5 ng ml-1 at the highest infusion rate. These results suggest that measurements of plasma Nt-methylhistamine are unlikely to provide a useful index of histamine release into the circulation.
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PMID:Histamine and Nt-methylhistamine in the circulation during intravenous infusion of histamine in normal volunteers. 321 6

Postural tachycardia syndrome (POTS) is a disabling condition that commonly affects otherwise normal young females. Because these patients can present with a flushing disorder, we hypothesized that mast cell activation (MCA) can contribute to its pathogenesis. Here we describe POTS patients with MCA (MCA+POTS), diagnosed by episodes of flushing and abnormal increases in urine methylhistamine, and compared them to POTS patients with episodic flushing but normal urine methylhistamine and to normal healthy age-matched female controls. MCA+POTS patients were characterized by episodes of flushing, shortness of breath, headache, lightheadedness, excessive diuresis, and gastrointestinal symptoms such as diarrhea, nausea, and vomiting. Triggering events include long-term standing, exercise, premenstrual cycle, meals, and sexual intercourse. In addition, patients were disabled by orthostatic intolerance and a characteristic hyperadrenergic response to posture, with orthostatic tachycardia (from 79+/-4 to 114+/-6 bpm), increased systolic blood pressure on standing (from 117+/-5 to 126+/-7 mm Hg versus no change in POTS controls), increased systolic blood pressure at the end of phase II of the Valsalva maneuver (157+/-12 versus 117+/-9 in normal controls and 119+/-7 mm Hg in POTS; P=0.048), and an exaggerated phase IV blood pressure overshoot (50+/-10 versus 17+/-3 mm Hg in normal controls; P<0.05). In conclusion, MCA should be considered in patients with POTS presenting with flushing. These patients often present with a typical hyperadrenergic response, but beta-blockers should be used with great caution, if at all, and treatment directed against mast cell mediators may be required.
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PMID:Hyperadrenergic postural tachycardia syndrome in mast cell activation disorders. 1571 Jul 81

Recurrent, pulseless-electrical-activity (PEA) cardiac arrests were the novel presentation of untreated systemic mastocytosis in an 85-year-old woman who lacked cutaneous findings of mastocytosis. Despite prior implantation of a dual-chamber cardiac pacemaker 3 weeks previously for similar spells, she experienced a PEA arrest accompanied by flushing, increased urinary N-methylhistamine excretion and serum tryptase values on the day of presentation to our clinic. Bone marrow biopsy findings conducted to rule out breast cancer metastases showed 30% mast cell infiltration, aberrant expression of CD25 and a positive c-kit Asp816Val mutation. Treatment with a combination of H1 and H2 receptor blockers reduced flushing and eliminated hypotension. Maintenance medication included aspirin, cetirizine, ranitidine, montelukast, oral cromolyn sodium and an epinephrine autoinjector (as needed). At 6-month follow-up, the patient remained free of PEA arrests, flushing, or any clinical signs of mastocytosis or mast cell degranulation. PEA cardiac arrests may therefore be a presenting sign of untreated systemic mastocytosis.
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PMID:Presentation of untreated systemic mastocytosis as recurrent, pulseless-electrical-activity cardiac arrests resistant to cardiac pacemaker. 2433 43