环孢素A、雷公藤内酯醇及红霉素与5-脂氧合酶产物的关系

目的 探索环孢素A、雷公藤内酯醇及红霉素对5-脂氧合酶的影响及建立相应的药效学方法。方法 采用反相高效液相色谱法检测5-脂氧合酶产物——白三烯B4和5-羟花生四烯酸量的变化来反映该酶活性的改变。结果 环孢素A可抑制白三烯B4和5-羟花生四烯酸的生成,呈剂量依赖性,IC₅₀值分别为38.0和0.96μg/mL。雷公藤内酯醇(T₀)可抑制白三烯B4和5-羟花生四烯酸的生成,呈剂量依赖性,IC₅₀值分别为2.3×10^-6和1.14×10^-6μg/mL。红霉素无剂量依赖性。结论 雷公藤的抗炎作用与抑制5-脂氧合酶活性有关,环孢素A的抑制浓度超出了其药理浓度,无实际意义,红霉素氧合酶活性无影响。     

Nonsteroidal topical treatment of inflammatory dermatoses

Reports of local and systemic complications from topically applied corticosteroids used in the treatment of inflammatory dermatoses warrant a re-examination of other methods of therapy. The specific measures suggested in this paper for treating seborrheic dermatitis, psoriasis, and atopic dermatitis may also be applied to eczematous eruptions that are in similar stages of development.     

Nonsteroidal antiinflammatory drug-induced pseudoporphyria: a case series

Background: Pseudoporphyria is a diagnosis that is used when porphyria-like clinical lesions arise in the setting of normal porphyrin levels. This condition was first described in the 1960s and was initially related to the use of certain antibiotic drugs. In 1985, pseudoporphyria was first attributed to the use of nonsteroidal antiinflammatory drugs (NSAIDs). Subsequently, a host of NSAIDs and other drugs have been found to elicit the same clinical entity. The exact mechanism by which certain drugs create clinical lesions resembling porphyria cutanea tarda or erythropoietic protoporphyria is still unknown. A phototoxic mechanism is hypothesized. Objective: We describe six patients diagnosed with pseudoporphyria and detail the diagnostic tests leading to the eventual diagnosis. Results: The patients ranged in age from 27 to 59 years and had a female:male predominance of 2:1. The offending NSAID was DayPro (oxaprozin) for three of the patients, Relafen (nabumetone) for two of the patients, and Aleve (naproxen) for one patient. For each patient, histology and immunofluorescence was either consistent with the diagnosis of porphyria cutanea tarda or nonspecific, while serum, stool, and urine porphyrins did not support that diagnosis. Withdrawal of the offending agent provided relief from the clinical symptoms for each patient. None of our patients were rechallenged with the putative offending drug. However, prolonged avoidance has provided a sustained remission from symptoms in all six patients.Conclusions: Pseudoporphyria is a relatively rarely reported condition. Clinical suspicion with appropriate laboratory and histopathologic findings help to make this diagnosis, and exclude true porphyrias. Rechallenge with the offending drug to produce symptom relapse has been proposed to be helpful in confirming this diagnosis of exclusion. Since all 6 patients with drug-induced pseudoporphyria experienced resolution of their symptoms after discontinuing the offending agent, we propose that this clinical correlation alone is sufficient to confirm this diagnosis. Our observation of six new cases of NSAID-induced pseudoporphyria over a two-year interval suggests that this is not a rare entity.     

Anti-inflammatory activity of tetracyclines

Tetracyclines are known to exhibit multiple significant anti-inflammatory actions. This article describes the mechanisms of this anti-inflammatory activity, such as inhibition of chemotaxis, granuloma formation, and protease. The article also discusses the effectiveness of tetracyclines in treating such diseases as acne vulgaris, rosacea, bullous dermatoses, granulomatous disease, and livedo vasculitis.     

Anti-inflammatory and immune-regulatory mechanisms prevent contact hypersensitivity to Arnica montana L

Sesquiterpene lactones (SL), secondary plant metabolites from flowerheads of Arnica, exert anti-inflammatory effects mainly by preventing nuclear factor (NF)-kappaB activation because of alkylation of the p65 subunit. Despite its known immunosuppressive action, Arnica has been classified as a plant with strong potency to induce allergic contact dermatitis. Here we examined the dual role of SL as anti-inflammatory compounds and contact allergens in vitro and in vivo. We tested the anti-inflammatory and allergenic potential of SL in the mouse contact hypersensitivity model. We also used dendritic cells to study the activation of NF-kappaB and the secretion of interleukin (IL)-12 in the presence of different doses of SL in vitro. Arnica tinctures and SL potently suppressed NF-kappaB activation and IL-12 production in dendritic cells at high concentrations, but had immunostimulatory effects at low concentrations. Contact hypersensitivity could not be induced in the mouse model, even when Arnica tinctures or SL were applied undiluted to inflamed skin. In contrast, Arnica tinctures suppressed contact hypersensitivity to the strong contact sensitizer trinitrochlorobenzene and activation of dendritic cells. However, contact hypersensitivity to Arnica tincture could be induced in acutely CD4-depleted MHC II knockout mice. These results suggest that induction of contact hypersensitivity by Arnica is prevented by its anti-inflammatory effect and immunosuppression as a result of immune regulation in immunocompetent mice.     

Anti-inflammatory activity of antifungal preparations

Background Although steroid/antifungal combination medications are used extensively, they are associated with potential disadvantages. Antifungal preparations possessing inherent anti-inflammatory activity, leading to rapid symptomatic relief while providing mycologic cure, would be very useful. Objective Our purpose was to investigate the anti-inflammatory activity of proprietary antifungal preparations in an in vivo, human experimental model. Methods Using a double-blind, controlled protocol, we assessed the comparative ability of antifungal preparations to suppress the expected delayed erythema response following in vivo human exposure to ultraviolet B (UVB) irradiation generated by a solar stimulator. Results Currently available allylamine preparations and ciclopirox olamine proved to be the most anti-inflammatory, while ketoconazole was intermediate in anti-inflammatory activity under these experimental conditions. These agents were superior to oxiconazole, econazole, and 2.5% hydrocortisone. Conclusions Some antifungal preparations possess inherent anti inflammatory activity, although the exact mechanism remains uncertain.     

Anti-inflammatory properties of an oxidized sterol

A polar photoproduct of cholesterol oxidation, 7-ketocholesterol, was able to inhibit in a dose-dependent manner the mouse ear-swelling response to irritants such as croton oil or cantharidin. Its anti-inflammatory properties were much less than equivalent concentrations of hydrocortisone, but the oxidized sterol did not induce any systemic effects (as measured by thymolytic activity), as did topical hydrocortisone. It is concluded that 7-ketocholesterol has weak anti-inflammatory activity, and its mode of action may be different from that of glucocorticoids.     

Anti-inflammatory effects of 13-cis-retinoic acid

Summary Sixteen patients with acne conglobata, acne fulminans, and acne tetrade were treated orally with 13-cis-retinoic acid, 1–2 mg/kg body weight for 12 weeks. A maintenance dose of 0.5 mg/kg in ten cases and the use of no further medication in six other cases for an additional 12 weeks followed. A 40% potassium iodide ointment was used on the upper back under occlusive dressing conditions to induce an inflammatory reaction. Four inflammatory parameters were assessed in all subjects before and during oral treatment: erythema (0–2+), edema (0–2+), papules (numbers), and pustules (numbers).All patients showed excellent improvement. Additionally, the inflammatory reaction in all patch-tests was significantly reduced: erythema from 1.13 to 0.34 (P0.01); edema from 1.06 to 0.25 (P0.0005); papules from 6.75 to 1.86 (P0.01); and pustules from 10.44 to 1.56 (P0.0025).We suggest that 13-cis-retinoic acid acts as a strong anti-inflammatory agent in addition to its known function as a sebostaticum.This work was supported in part by Grant No. P158/6 from the Deutsche Forschungsgemeinschaft