ABSTRACT
BACKGROUND: Rosacea is a chronic inflammatory skin disease. Characteristic vascular changes in rosacea skin include enlarged, dilated vessels of the upper dermis and blood flow increase. Brimonidine is approved for symptomatic relief of the erythema of rosacea. It acts by selectively binding to α2-adrenergic receptors present on smooth muscle in the peripheral vasculature, resulting in transient local vasoconstriction. OBJECTIVES: To provide further evidence of the anti-inflammatory potential of brimonidine across preclinical models of skin inflammation and its ability to decrease the neutrophil infiltration in human skin after ultraviolet light exposure. METHODS: The anti-inflammatory properties of brimonidine through modulation of the vascular barrier function were assessed using in vivo neurogenic vasodilation and acute inflammatory models and a well-described in vitro transmigration assay. A clinical study assessed the neutrophil infiltration in human skin after exposure to UV in 37 healthy Caucasian male subjects. RESULTS: In vitro, brimonidine affects the transmigration of human neutrophils through the endothelial barrier by modulating adhesion molecules. In vivo, in the mouse, topical treatment with brimonidine, used at a vasoconstrictive dose, confirmed its anti-inflammatory properties and prevented leucocyte recruitment (rolling and adhesion) mediated by endothelial cells. Topical pretreatment with brimonidine tartrate 0.33% gel once a day for 4 days significantly prevented neutrophil infiltration by 53.9% in human skin after exposure to UV light. CONCLUSION: Results from in vitro, in vivo and from a clinical study indicate that brimonidine impacts acute inflammation of the skin by interfering with neurogenic activation and/or recruitment of neutrophils.
Subject(s)
Anti-Inflammatory Agents/administration & dosage , Brimonidine Tartrate/administration & dosage , Rosacea/drug therapy , Skin/blood supply , Skin/drug effects , Administration, Cutaneous , Adolescent , Adult , Animals , Cell Movement , Dermatitis/drug therapy , Endothelial Cells/drug effects , Erythema/drug therapy , Human Umbilical Vein Endothelial Cells , Humans , Inflammation , Male , Mice , Middle Aged , Neutrophils/cytology , Neutrophils/drug effects , Proteome , Ultraviolet Rays , Vasodilation , Young AdultABSTRACT
BACKGROUND: There are few studies on the natural history of acne lesions including the antecedents of atrophic scars.
STUDY DESIGN: Prospective study of relationship between primary (papules, pustules, comedones) and secondary lesions (atrophic scars, macular erythema, and hyperpigmentation) over 6 months. Subjects (n=32) had moderate facial acne including 10 or more atrophic acne scars and were their own control via randomized split-face design. Lesions were mapped 2x/week for 2 months and every 2 weeks thereafter until month 6 to track pathogenic progression.
RESULTS: Clinical assessment showed acne scars continuously forming throughout the 6-month study period. While the majority (66.2%) of these scars did not resolve by study endpoint, the remainder were transient. The likelihood of a scar developing from a primary acne lesion was 5.7%, and almost all scars arose from erythematous macules or hyperpigmentation (83%) and some (16%) developed directly from papules and pustules. Duration of papules was a key factor in the risk of scarring. The majority (81.7%) of the scars remaining at 6 months were still present at 2-year follow-up.
CONCLUSIONS: Atrophic acne scars continuously form, some resolve, and evolve primarily from inflammatory and post-inflammatory lesions. Clinicians should closely monitor patients with macular erythema for scarring.
J Drugs Dermatol. 2017;16(6):566-572.
.Subject(s)
Acne Vulgaris/complications , Acne Vulgaris/pathology , Cicatrix/etiology , Cicatrix/pathology , Erythema/complications , Erythema/prevention & control , Adolescent , Adult , Atrophy/pathology , Double-Blind Method , Face/pathology , Female , Follow-Up Studies , Humans , Hyperpigmentation/pathology , Inflammation/pathology , Male , Prospective Studies , Skin/pathology , Treatment Outcome , Young AdultABSTRACT
The determination of chemiluminescent intensity of reporter gene expression in vivo is generally disturbed by the presence of hemoglobin. Current methods consist in using perfusion to eliminate blood from investigated tumors or organs. In this work we propose a simple method to overcome this difficulty. The method consists in establishing an absorbance-dependence plot of the ratio R% = phi/phi(0) between the chemiluminescent intensities measured when hemoglobin is present or absent. For every measurement of the luminescent intensity phi on sample containing blood, if the absorbance A of the hemoglobin is determined, it allows one to have the intensity ratio R% which in turn gives the corrected intensity phi(0) when the absorption by hemoglobin is eliminated. The method is particularly adapted for comparative measurements of transfection levels in tumors where perfusion cannot be easily performed.
