Background: Mast cells are involved in allergy and inflammation by secreting multiple mediators including histamine, cytokines and platelet-activating factor. Certain histamine 1 receptor antagonists have been reported to inhibit histamine secretion, but the effect on cytokine release from human mast cells triggered by allergic and other stimuli is not well known. We investigated the ability of rupatadine, a potent histamine 1 receptor antagonist that also blocks platelet-activating factor actions, to also inhibit mast cell mediator release. Methods: Rupatadine (1–50 μM) was used before stimulation by: (1) interleukin (IL)-1 to induce IL-6 from human leukemic mast cells (HMC-1 cells), (2) substance P for histamine, IL-8 and vascular endothelial growth factor release from LAD2 cells, and (3) IgE/anti-IgE for cytokine release from human cord blood-derived cultured mast cells. Mediators were measured in the supernatant fluid by ELISA or by Milliplex microbead arrays. Results: Rupatadine (10–50 μM) inhibited IL-6 release (80% at 50 μM) from HMC-1 cells, whether added 10 min or 24 h prior to stimulation. Rupatadine (10–50 μM for 10 min) inhibited IL-8 (80%), vascular endothelial growth factor (73%) and histamine (88%) release from LAD2 cells, as well as IL-6, IL-8, IL-10, IL-13 and tumor necrosis factor release from human cord blood-derived cultured mast cells. Conclusion: Rupatadine can inhibit histamine and cytokine secretion from human mast cells in response to allergic, immune and neuropeptide triggers. These actions endow rupatadine with unique properties in treating allergic inflammation, especially perennial rhinitis and idiopathic urticaria.

Coronary artery disease is associated with increased serum levels of cholesterol, triglycerides and LDL, but low levels of HDL. The most potent agent capable of reversing this trend is the vitamin nicotinic acid (niacin). However, compliance even with extended-release preparations and addition of acetylsalicylic acid (ASA) is hampered by the development of a feeling of erythema and burning ("flush"), especially on the face. We recently showed that the natural flavonoids quercetin and luteolin can eliminate "flush", as well as inhibit both niacin-induced plasma prostaglandin D, (PGD z ) and serotonin increase in an animal model. We conducted a pilot clinical study in humans. Four normal male subjects received (a) 1 g immediate release niacin either alone or after (b) the dietary formulation (Algonot-plus") containing 150 mg quercetin per capsule. Subjects completed a visual scale (l=no, 5=worst response) symptom assessment. Erythema and burning sensation scores were both 4.75±0.50 and lasted for 3.63±1.11 hours. After Algonot-plus" administration, both scores were reduced to 2.5±0.58 and lasted for only 1.68±O.70 hours. Quercetin also inhibited methylnicotinate-induced human mast cell PGD z release. These preliminary results suggest that quercetin could reduce niacin-induced "flush" in humans.Ingestion of the B 3-vitamin niacin (nicotinic acid) has been repeatedly shown to improve hypercholesterolemia and other lipoprotein abnormalities, while it also-increases HOL levels (1). Moreover, the combination of niacin with lovastatin has been shown to be superior to either agent alone (2-4). However, a serious limiting adverse effect is the development of significant facial erythema and warmth, known as "flush" that is more intense with immediate release than with extended release niacin (2, 5-6). Moreover, most of the over-the-counter formulations either do not contain sufficient niacin to have any effect or contain niacin metabolites that are ineffective (7).Niacin is thought to induce flush by stimulating the release of prostaglandin 02 (PG0 2) from the skin (8-9), most likely from dermal macrophages (10). However, co-administration of acetylsalicylic acid (ASA) does not reduce PGD 2 levels more than about 30% (II). Other measures used to reduce flush have included avoidance of alcohol and spicy foods with little benefit (12).We recently used a rat model of flush (13) and showed that niacin-induced skin vasodilation was accompanied by increased plasma PGD 2 , but also serotonin increases, both of which were inhibited along with the flush by the f1avonoids quercetin and luteolin (14). We therefore conducted a pilot clinical trial to investigate if a quercetin containing dietary supplement could inhibit niacin-induced flush in humans. MATERIALS AND METHODS MaterialsImmediate release macin caplets (250 mg each, SLO-NIACIN

A spider bite may represent a possible causative factor of AGEP. A spider's venom contains sphingomyelinase that stimulates the release of IL8 and GM-CSF, which are involved in AGEP pathogenesis. Whether or not the con-current use of antibiotics has an effect in AGEP appearance when combined with a spider's venom, cannot be excluded.

Although FA causes severe anaphylactic episodes, almost 50% of individuals who experience symptoms perceived as FA do not seek medical advice. Awareness programmes must be carried out in order to increase consciousness about this potentially fatal medical condition.