Toxicity of Polyaromatic Hydrocarbons other than Benzo(A)Pyrene: A Review

Abstract

Much of the discussion about coal tar concentrates on the toxicological properties and safety limits of benzo(a)pyrene (BP). This chemical has been studied in depth by research scientists and a great deal of relevant data has been published.

In addition to BP there are many more polycyclic aromatic hydrocarbons (PAH) present in coal tar and of these, some of the commonest are benzo(a)anthracene (BA), benzo(b)fluoranthene (BbF), benzo(k)-fluoranthene (BkF), and dibenz(a,h)anthracene (DBA).

The purpose of this review is to survey the published data relating to the toxicity and safety of each of these chemicals. Although the review will be examining the safety profile of the individual chemicals, there is evidence to show that when PAH are in combination, as in the case of a complex mixture such as coal tar, their individual biological activity can be modified. This will be discussed in more detail.

Much of the reported data regarding the safety of these chemicals ha /e been related to their ingestion or inhalation, especially in animals. Very few data could be found regarding the safety of the chemicals and their absorption and metabolism after topical application. This report will concentrate on dermal application.

Where the effects of PAH in humans have been described, these generally have been through extrapolation of data obtained from studies with coal tar or coal tar products.     

Acitretin and treatment of the oral leucoplakias. A model to have an active molecules release

AIMS: The aim of this study was to investigate the effectiveness of acitretin in a new topical formulation (mucoadhesive two-layer tablets) for the treatment of oral leucoplakias. METHODS: Twenty-one volunteers, 16 men, five women, with oral leucoplakia (histologically diagnosed), were included in this double-blind placebo-controlled study. Patients were randomized in three groups (A, B, C) of seven patients each. Groups A and B received tablets with different in vitro release profiles, and group C subjects (controls) received tablets without acitretin. The acitretin dose was 20 mg/day (two 10 mg tablets daily). Serum aspartate aminotransferase, alanine aminotransferase, cholesterol and triglycerides were evaluated before and after treatment. At the end of therapy the concentrations of acitretin in plasma, saliva and tissue were measured by high-performance liquid chromatography. RESULTS: At the end of the study 71% (groups A and B) of patients showed clinical remission or marked improvement. No improvement was noted in the control subjects (group C). These results were further confirmed by histological findings. There were no significant changes in laboratory values in the three groups. The acitretin concentration in plasma and tissue ranged from 0 to 50 mg with no difference between groups A and B, and it was very high in saliva (ranging from 4.9 to 43 mg) with higher concentrations in group A than in group B (due to a longer adhesion time in group A). Patients' compliance was excellent. The results show that mucoadhesive tablets of topical acitretin are efficacious in the treatment of oral leucoplakia without systemic side-effects.     

Cyclosporin A treatment in severe childhood psoriasis

Though used occasionally, systemic therapies in severe childhood psoriasis have not been systematically investigated. Cyclosporin A (CysA) is effective in adults with severe psoriasis but there are no extensive data regarding the efficacy and safety of its use in childhood psoriasis. In this paper, we describe six children aged between 11 months and 13 years (average: 7.6 years) treated with CysA microemulsion formulation for severe psoriasis, who had been unresponsive to other treatments. The CysA dose ranged from 2 to 4 mg/kg/day, for periods varying from 8 to 105 weeks (mean: 54 weeks). Dose tapering was gradual after lesion improvement and adjusted according to clinical response. Adjuvant therapy with topical steroids, vitamin D3 ointments, coal tar preparations or anthralin was used in all children. Acitretin was used in three patients for short periods. The children were regularly monitored for serum renal and liver function and blood pressure. Improvement of skin lesions was achieved after between 4 and 30 (mean: 12) weeks of treatment, with complete remission in three children. Relapse of lesions occurred in the other children during CysA reduction, but they responded to a dose increase. The treatment was found to be well tolerated and with no significant side-effects. CysA can be used in carefully selected and monitored patients and may represent an alternative tool for severe episodes of psoriasis in children, when other therapies are unsuccessful.     

阿维A对寻常型银屑病患者血清TNF—α及IL-8的影响

目的确定肿瘤坏死-α（TNF-α）及白介素-8（IL-8）在寻常型银屑病发病中的作用及阿维A对其的调节作用。方法应用双抗体夹心酶联免疫吸附法（ELISA）检测30例寻常型银屑病患者经阿维A治疗前后外周血清中TNF-α及IL-8的水平。结果寻常型银屑病患者血清中TNF-α、IL-8的水平较正常人对照组显著增高（P〈0．01）。治疗后血清中TNF-α、IL-8较治疗前显著下降（P〈0．01）。结论阿维A可通过调节血清中TNF-α、IL-8水平而起到治疗作用。     

血浆微RNA-126表达水平对银屑病患者阿维A、甲氨蝶呤联合光疗应答的预测价值

目的 探索接受阿维A、甲氨蝶呤联合光疗治疗的银屑病患者血浆微RNA-126（miRNA-126）表达水平在治疗前后的变化及其对于疗效的预测作用。方法 连续纳入196例接受阿维A、甲氨蝶呤联合紫外线光疗治疗的中重度银屑病患者作为研究对象,并纳入同期200名健康志愿者作为对照。分别于基线期及治疗1个月、3个月和6个月后采集银屑病患者的血液样本,在入组后采集健康受试者的血液样本,测量血浆miRNA-126表达水平。采用银屑病皮损面积及严重度指数（PASI）评估疾病严重程度,PASI 50应答（治疗后PASI与基线期相比下降50%）和PASI 75应答（治疗后PASI与基线期相比下降75%）评估治疗效果。采用Spearman等级相关检验分析患者血浆miRNA-126表达水平与PASI的相关性,受试者工作特征（ROC）曲线评估miRNA-126相对表达量对银屑病的诊断价值,单因素和多因素logistic回归模型分析PASI 50和PASI 75应答的影响因素。结果 基线期银屑病患者血浆中miRNA-126呈低表达,其表达水平与患者PASI呈负相关（r=-0.222,P=0.002）。ROC曲线分析结果显示血浆miRNA-126表达水平可以较好地分辨银屑病患者与健康对照（曲线下面积为0.700）。治疗1个月、3个月和6个月后,银屑病患者血浆miRNA-126表达水平均比基线期增高（P<0.01）,PASI 50应答率分别为7.1%（14/196）、37.2%（73/196）及64.8%（127/196）,PASI 75应答率分别为1.5%（3/196）、14.3%（28/196）及35.7%（70/196）。PASI 50应答和PASI 75应答患者基线期血浆miRNA-126相对表达量高于未应答患者（P<0.05）。Logistic回归分析结果显示基线期血浆miRNA-126相对表达量与患者PASI 50应答和PASI 75应答独立负相关。结论 银屑病患者血浆miRNA-126表达水平在接受阿维A、甲氨蝶呤联合紫外线光疗治疗后逐渐升高,且其基线期表达水平与治疗效果独立负相关。     

Effects of acitretin on spermatogenesis of rats

In this experimental study the possible effects of the acitretin on the spermatogenesis of the rats were investigated histopathologically. Thirty-nine male adult Wistar albino rats were divided into 3 groups as two experimental groups and one control group. The first group consisting 14 rats were applied orally standard dose (0.75 mg/kg/day) acitretin and the second group consisting 16 rats were applied high dose (1.5 mg/kg/day) acitretin. Acitretin was given within dimetil sulphoxide (DMSO), which was diluted with saline solution as a ratio of 1/10, in order to increase its solubility. The control group consisting 9 rats were given only saline solution including DMSO for 8 weeks. After 8 weeks of the administration, half of the rats in the first and second groups and the entire control group were sacrificed under deep ether anaesthesia and bilateral orchiectomy was made. The remaining rats were compared with the control group using a similar method at the end of 8 weeks of wash-off period. The orchiectomy materials were histopathologically evaluated under the light microscope for spermatogenesis according to parameters including spermatogenetic activity, spermatogenetic organization, seminiferous tubular diameter, interstitial Leydig cells and fibroblasts. The groups, which were evaluated at the end of the 8(th) and 16(th) weeks, were compared with the control group regarding the mentioned parameters and no statistical significance was observed among the groups. In our study it was concluded that the standard and high doses of acitretin do not have any effect on the spermatogenesis of the rats.     

阿维A胶囊联合卡介菌多糖核酸治疗顽固性扁平疣疗效观察

目的:观察阿维A胶囊联合卡介菌多糖核酸治疗顽固性扁平疣的临床疗效。方法:将93例扁平疣患者随机分成两组。治疗组47例,对照组46例,两组患者均肌注卡介菌多糖核酸注射液1ml,隔日1次,外用0.1%维A酸乳膏;治疗组同时口服阿维A胶囊,20mg/天,治疗后4、8周末观察疗效。结果:对照组治疗4、8周末的有效率分别为58.70%和71.74%,治疗组分别为78.72%和89.36%,两组患者4、8周末的有效率比较均有统计学意义(均P0.05),且治疗组的复发率明显低于对照组(P0.05)。结论:阿维A胶囊联合卡介菌多糖核酸治疗顽固性扁平疣疗效确切,复发率低。     

The effect of various methods of psoriasis treatment on somatotrophin axis hormones in serum

Objective: To investigate the effect of pharmacotherapy and phototherapy on the concentration of hormones of the somatotrophin axis [growth hormone (GH), insulin‐like growth factor‐I (IGF‐I) and insulin‐like growth factor binding protein‐3 (IGFBP‐3)] in the serum of patients with psoriasis in exacerbation and remission. Methods: GH and IGFBP‐3 in serum were determined by immunoradiometric assay (IRMA), and IGF‐I concentrations – by radioimmunological assay (RIA). The dermatological state was assessed by the psoriasis area and severity index (PASI). Results: There was no significant difference in the GH concentrations in patients both in exacerbation and remission, irrespective of therapy applied. However, in the group treated by phototherapy a significant increase in IGFBP‐3 secretion was observed, whereas in the group treated with cyclosporin A – a significant increase in IGF‐I secretion was observed in remission. Conclusion: Different methods of treatment have different effects on the secretion of somatotrophin axis hormones, but generally the hormone concentrations do not return to the values observed in healthy people. The therapeutic actions of the drugs concerned are not fully known and require further investigations.     

清肺凉血汤联合阿维A治疗寻常型银屑病36例

目的：观察清肺凉血汤联合阿维A治疗寻常型银屑病的临床疗效。方法：将72例寻常型银屑病患者随机分为治疗组和对照组各36例,治疗组给予清肺凉血汤联合阿维A治疗,对照组给予阿维A治疗。2组均以治疗4周为1个疗程,共治疗2个疗程。观察临床症状、不良反应和复发率。结果：总有效率治疗组为91.67%,对照组为77.78%,2组比较差异显著（P〈0.05）。2组治疗后PASI评分治疗组与对照组相比差异显著（P〈0.05）。结论：清肺凉血汤联合阿维A治疗寻常型银屑病具有较好的疗效和安全性。     

Treatment of verrucous carcinoma of vulva with acitretin

We describe a 60-year-old patient with verrucous carcinoma of the vulva, which recurred 6 years after simple vulvectomy and radiotherapy. Treatment with acitretin led to significant improvement and ongoing disease control has been achieved with low-dose maintenance therapy of 10 mg acitretin daily.