The sensitizing potential of di-(meth) acrylates based on bisphenol A or epoxy resin in the guinea pig

Most composite materials in dentistry used today, contain resins based on dimethacrylates. BIS-GMA [2,2-bis-(4-(2-hydroxy-3-methacryloxypropoxy)phenyl)propane], the addition reaction product of bisphenol A and glycidyl methacrylate or an epoxy resin and methacrylic acid, is used most extensively. More recently, dimethacrylates based on bisphenol A, with various chain lengths have appeared on the market as a substitute for or in addition to BIS-GMA. Such compounds are BIS-MA [2,2-bis-(4-(methacryloxy)phenyl)propane], BIS-EMA [2,2-bis-(4-(2-methacryloxyethoxy)phenyl)propane] and BIS-PMA [2,2-bis-(4-(3-methacryloxypropoxy)phenyl)propane]. Increasing interest in the radiaton cure of coatings and printing inks have focused attention on these substances and on epoxy diacrylates as radiation-curable resins. The sensitizing capacity of the different acrylates based on bisphenol A or epoxy resin have been investigated with the guinea pig maximization test. The pattern of simultaneous reactivity of the compounds was also studied. Epoxy diacrylate [2,2-bis-(4-(2-hydroxy-3-acryloxy-propoxy)phenyl)propane], BIS-EMA and BIS-MA are shown to be strong sensitizers, while the linear fraction of BIS-GMA and its isomers and BIS-PMA have none or a low sensitizing capacity. The impurities in the BIS-GMA and BIS-MA batches seem to have high allergenic potential. These results stress the importance of a pure substance when discussing allergenicity and cross reactions.     

Dinitrohalobenzenes: evaluation of relative skin sensitization potential using the local lymph node assay

The dinitrohalobenzenes are known to cause skin sensitization and have been used in many seminal investigations of the relationships between physicochemical characteristic and sensitizing potential. The electrophilic theory of skin sensitization implies that contact allergic potential should correlate positively with the ability of chemicals to react with proteins to form immunogenic hapten-protein conjugates. It is intriguing, therefore, that previous studies in guinea pigs and mice have suggested that such correlations do not apply to dinitrohalobenzenes. To address this, we have examined, using the murine local lymph node assay (LLNA), the sensitizing activity of 2,4-dinitroiodobenzene (DNFB), 2,4-dinitrochlorobenzene (DNCB), 2,4-dinitrobromo-bezene (DNBB) and 2,4-dinitroiodobenzene (DNIB). In contrast to previous investigations, it was found that the ability of these chemicals to provoke responses in the LLNA correlated closely with their reported protein reactivity. On the basis of these data, it is proposed that dinitrohalobenzenes conform to the electrophilic theory of skin sensitization and that they should be regarded as direct acting haptens.     

Dichloronitrobenzene: a reappraisal of its skin sensitization potential

Unlike the closely related chemical dinitrochlorobenzene (DNCB), which is a very strong contact allergen, dichloronitrobenzene (DCNB) has been widely regarded as a non-allergen and, as such, a useful control for its strongly sensitizing counterpart. Nevertheless, it is still an organic chemical species readily capable of penetrating skin and, rather than being regarded as completely inert, it has even been suggested to react with the immune system in such a way that it induces specific tolerance to its chemical structure. We investigated whether DCNB was in reality a non-allergen, or rather merely a weak contact sensitizer. In both a rigorously conducted guinea pig maximization test and in a modified murine local lymph node assay. DCNB was demonstrated lo possess weak sensitizing activity. On this basis, DCNB cannot be regarded as inert with respect to contact allergic potential, and is therefore inappropriate as a negative control in studies of skin sensitization     

The sensitizing capacity of Alstroemeria cultivars in man and guinea pig. Remarks on the occurrence, quantity and irritant and sensitizing potency of their constituents tuliposide A and tulipalin A (alpha-methylene-gamma-butyrolactone)

Dermatitis in 8 female nursery workers handling Alstroemeria ligtu cultivars has been proven in 6 cases to be of allergic origin. Epicutaneous tests with cut flower extracts as well as with the isolated and purified sensitizer were positive. Successful animal experiments corroborated the sensitising capacity of Alstroemeria cultivars. The responsible but unstable contact allergen. α-methylene-γ-butyrolactone (tulipalin A), was found in short ether extracts of flower petals in concentrations up to 18%. Due to its instability, subsequent extractions were performed with methanol, yielding the sensitising constituent after purification in the glucosidic form (tuliposide A). This could be stored at room temperature for longer periods without loss of activity. Tuliposide A was determined in specimens of Alstroemeria ligtu cultivars of 14 different origins of various colours: its content varied between 1 and 2%. Direct testing of the plant material in human patients carries the risk of false positive reactions and active sensitization, as the threshold for both forms of the allergen is very high. Only a concentration of 0.01% can be considered safe.     

Experimental study of the potential for contact sensitization and cross-reaction of imidazole antifungals

We examined the potential for contact sensitization of miconazole nitrate and croconazole hydrochloride and the cross-reaction between them in guinea pigs by the maximization test of Magnusson and Kligman. Contact sensitivity was induced by croconazole hydrochloride in 5 out of 7 animals which, after being injected with 5% croconazole hydrochloride, underwent a closed patch with 25% croconazole hydrochloride. Contact sensitivity was not induced by miconazole nitrate. The 5 animals sensitized to croconazole hydrochloride were tested with 8 other imidazole antifungals and positive reactions were observed to oxiconazole nitrate in 2 of the 5 animals. This response may be a cross-reaction.     

An investigation of the allergenic constituents of Cladonia stellaris (Opiz) Pous & VeŽda ('silver moss', 'reindeer moss' or 'reindeer lichen')

The sensitizing potency of Cladonia stellaris ('reindeer lichen silver moss') extracts was determined in guinea pigs by a modified FCA (Freund's complete adjuvant) lest. The lichen showed a moderate sensitizing potency. Similar investigations with pure common lichen constituents revealed a moderate sensitizing potency for fumarprotocetraric acid and atranorin and a weak one for evernic acid, stictic acid and both forms of usnic acid. Although generallt weak, (–)-usnic acid was at least 2 × stronger than (+)-usnic acid. After separation of the Cladonia ether extract into 'usnic-acid-free' and 'usnic-acid-containing' fractions, perlatolic acid was identified as the main allergenic constituent of the 'usnic-acid-free fraction'. Stictic, evernic. fumarprotocetraric acid and atranorin were not detectable. Lichens and lichen products generally possess a weak to moderate sensitizing capacity. Compared with common sensitizers of occupational and environmental importance, these products play only a minor role.     

Allergic contact dermatitis in shiitake (Lentinus edodes (Berk) Sing) growers

A 42-year-old female shiitake grower was investigated to clarify the etiology of skin lesions which developed during the planting of shiitake hyphae into bed logs. She complained of repeated eczematous skin lesions during the planting season, from March to July, for 10 years. She handled 7,000 pieces of small conic blocks made of beech, with shiitake hyphae attached to their surface, per day, and 300,000 pieces altogether per season. She was positive on patch testing with extracts of shiitake hyphae. In contrast, female shiitake growers with skin lesions associated with work other than planting, and without skin lesions, were negative on patch testing to the hyphae. Moderate allergenicity was observed to extracts of shiitake hyphae in a guinea pig maximization test. These findings indicated the etiology of skin lesions in shiitake growers to be allergic contact dermatitis induced by shiitake hyphae.     

308 nm准分子激光对豚鼠皮肤黑素细胞的影响

目的:研究308 nm准分子激光对皮肤色素沉着的诱导作用,为其治疗白癜风提供科学依据.方法:以正常棕黄色豚鼠皮肤为实验模型,用不同剂量的308 nm准分子激光进行照射,分别采用肉眼评估、黑素细胞染色(Imokawa法)及黑素颗粒染色(Fontana-Masson法)研究该激光的致色素沉着作用;对不同照射剂量组豚鼠皮肤中的一氧化氮合酶(NOS)进行免疫组化染色,间接观察黑素调节因子一氧化氮(NO)的变化情况;苏木精-伊红染色观察表皮组织学改变.结果:各组的色素沉着评分、平均黑素数量以及多巴阳性黑素细胞数之间差异均具有统计学意义(P＜0.05).结论:308 nm准分子激光可诱导豚鼠皮肤色素沉着,且这种效应随着照射剂量的上升而增强.     

豚鼠皮肤球形马拉色菌感染模型的建立

目的：建立皮肤球形马拉色菌感染的动物模型。方法：分别采用涂菌1次法、涂菌1次并皮下注射甲泼尼龙法、连续7d涂菌法3种方法诱导豚鼠皮肤感染球形马拉色菌。结果：连续7d涂菌法适合于此模型的建立，得到了满意的皮损及菌落数。结论：皮肤菌落计数能更直观、客观地反映药物的短期疗效，是评价皮肤球形马拉色菌感染模型较科学的指标。     

抗过敏性鼻炎甘辛喷雾剂的研究

目的研制复方甘草和辛夷(甘辛)鼻用抗过敏喷雾剂。方法以甘草提取物甘草甜素和辛夷花提取液为主药制备成鼻用喷雾剂,建立RP-HPLC测定甘草酸含量,以2.4-二异氰酸甲苯酯(TD I)介导的豚鼠超敏反应为模型,观察甘辛喷雾剂模型对过敏性鼻炎的疗效。结果制剂制备工艺可行,质量稳定,RP-HPLC对甘草酸铵含量测定结果可靠,重现性好;甘辛喷雾剂大小两个剂量组均在一定程度上使鼻黏膜上皮下嗜酸性粒细胞、淋巴细胞、浆细胞和嗜中性粒细胞减少,腺体增生和分泌亢进得到有效的抑制。结论甘辛喷雾剂可有效抑制超敏反应过程,保护鼻黏膜组织结构。