Assessment of intracellular cytokines and regulatory cells in patients with autoimmune diseases and primary immunodeficiencies — Novel tool for diagnostics and patient follow-up

Serum and intracytoplasmic cytokines are mandatory in host defense against microbes, but also play a pivotal role in the pathogenesis of autoimmune diseases by initiating and perpetuating various cellular and humoral autoimmune processes.     

Extracorporeal photochemotherapy for paediatric patients with graft-versus-host disease after haematopoietic stem cell transplantation

This study aimed to ascertain whether extracorporeal photochemotherapy (ECP) is an effective treatment for paediatric patients with refractory graft-versus-host disease (GVHD). From January 1992 to December 2000, 77 children (median age 8.6 years) with either acute (n = 33) or chronic (n = 44) GVHD, resistant to conventional immunosuppressive therapy, were treated with ECP in four Italian paediatric hospitals. After ECP, acute GVHD involving skin, liver and gut responded completely in 76%, 60% and 75% of patients respectively. The 5-year overall survival was 69% for responding patients vs 12% for non-responders (P = 0.001). Among the 44 children with chronic GVHD, 15 (44%) showed a complete response and 10 (29%) a significant improvement after ECP. The 5-year overall survival was 96% for responders vs 58% for non-responders (P = 0.04). Our results suggest that ECP is an effective treatment that may be useful in paediatric patients with either acute or chronic GVHD who have failed to respond to standard immunosuppressive therapy.     

聚氧乙烯蓖麻油增强锌酞菁光敏剂对小鼠肿瘤的光动力治疗作用

目的探讨聚氧乙烯蓖麻油（CrEL）作为磺酸基邻苯二甲酰亚胺甲基锌酞菁（ZnPcS2P2）的溶剂在移植性小鼠肿瘤及体外培养的肿瘤细胞的光动力治疗中的作用.方法荷U14肿瘤的小鼠,尾静脉注射ZnPcS2P224 h后,激光（670 nm）照射,继续饲养5 d后剥取肿瘤称质量;用体外培养的黑色素瘤B16细胞与含或不含CrEL的药物作用2 h后洗去药物,光辐射后继续培养24 h,测定药物对肿瘤细胞的杀伤作用.结果不含CrEL的锌酞菁对小鼠移植瘤的光动力抗癌作用弱,其光动力抗癌作用随CrEL含量增加而增强.ZnPcS2P2对体外培养的B16细胞的光动力杀伤作用,也明显依赖于CrEL的含量.结论CrEL能增强ZnPcS2P2的光动力抗肿瘤作用.     

两种CPD光敏剂对小鼠S180肉瘤的光动力杀伤效应

目的：比较新型光敏剂CPD4和CPD6对小鼠S180移植肉瘤的光动力学疗效。方法：给昆明小鼠接种S180肉瘤，建立移植肿瘤模型。将模型小鼠随机分成7组（n=8），分别为CPD4和CPD6中、低剂量组，血卟啉组，生理盐水对照组及未经任何治疗组。尾静脉注射给药，给药后20min以波长670nm激光垂直照射瘤区20min（血卟啉组照射60min）。治疗后30d将各组小鼠断颈处死，取瘤称质量并计算抑瘤率，做病理切片、常规染色，镜下观察形态学差异。结果：CPD4中、低剂量组的抑瘤率分别为54．5％，97．9％；CPD6低剂量组的抑瘤率为46．9％；血卟啉组的抑瘤率为55．8％．镜下观察各组切片形态学差异明显。CPD。低剂量组的疗效高于血卟啉组，亦高于同剂量CPD6组。CPD6低剂量组疗效与血卟啉组相近。结论：光动力学治疗对小鼠S180移植肉瘤有抑制作用，该研究可为生产治疗恶性肿瘤的新药提供科学的实验依据。     

Photodynamic modulation of cellular function

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Phototherapy and photochemotherapy of sclerosing skin diseases

The treatment of sclerosing skin diseases [systemic sclerosis, localized scleroderma, lichen sclerosus et atrophicus, sclerodermoid graft-vs.-host disease, scleredema adultorum (Buschke), scleromyxedema and necrobiosis lipoidica] is difficult and remains a great challenge. Numerous treatments, some with potentially hazardous side effects, are currently used with only limited success. The introduction of phototherapy and photochemotherapy for sclerosing skin diseases has considerably enriched the therapeutic panel and proven useful in a number of sclerosing skin diseases especially in localized scleroderma. Two phototherapeutic modalitites are used for the treatment of sclerosing skin diseases, long-wave ultraviolet A and psoralen plus ultraviolet A (PUVA). This article reviews current knowledge about the application of phototherapy and photochemotherapy to various sclerosing skin disorders.     

Determination of the minimal phototoxic dose and colorimetry in psoralen plus ultraviolet A radiation therapy

BACKGROUND: The use of an adequate initial dose of ultraviolet A (UVA) radiation for photochemotherapy is important to prevent burns secondary to overdosage, meanwhile avoiding a reduced clinical improvement and long-term risks secondary to underdosage. The ideal initial dose of UVA can be achieved based on the phototype and the minimal phototoxic dose (MPD). The objective measurement of constitutive skin color (colorimetry) is another method commonly used to quantify the erythematous skin reaction to ultraviolet radiation exposure. The aim of this study was to determine variations in MPD and constitutional skin color (coordinate L(*)) within different phototypes in order to establish the best initial dose of UVA radiation for photochemotherapy patients. METHODS: Thirty-six patients with dermatological conditions and 13 healthy volunteers were divided into five groups according to phototype. Constitutional skin color of the infra-axillary area was assessed by colorimetry. The infra-axillary area was subsequently divided into twelve 1.5 cm(2) regions to determine the MPD; readings were performed 72 h after oral administration of 8-methoxypsoralen (MOP) followed by exposure of the demarcated regions to increasing doses of UVA. Results: The majority of the participants were women (73.5%) and their mean age was 38.8 years. The MPD ranged from 4 to 12 J/cm(2) in phototypes II and III; from 10 to 18 J/cm(2) in type IV; from 12 to 24 J/cm(2) in type V and from 18 to 32 J/cm(2) in type VI. The analysis of colorimetric values (L(*) coordinate) and MPD values allowed the definition of three distinctive groups of individuals composed by phototypes II and III (group 1), types IV and V (group 2), and phototype VI (group 3). CONCLUSIONS: MPD and L(*) coordinate showed variation within the same phototype and superposition between adjacent phototypes. The values of the L(*) coordinate and the MPD lead to the definition of three distinct sensitivity groups: phototypes II and III, IV and V and type VI. Also, the MPD values bear a strong correlation to coordinate L(*) values. Mean MPD values described for each of the three major sensitivity groups were higher than the values commonly used in clinical settings for the different phototypes. Therefore, phototype alone is not a good parameter to define the initial UVA dose. MPD and colorimetry could be used in pre-treatment evaluation of patients who are to be submitted to photochemotherapy, in a non-invasive and more accurate way when compared with the classical phenotype clinical criteria.     

Anaphylaxis to 5-methoxypsoralen during photochemotherapy

Photochemotherapy is very effective for the treatment of skin diseases such as psoriasis, as well as for the prophylactic 'hardening' therapy of patients suffering from polymorphic light eruption. The photosensitizers most widely used for oral photochemotherapy are the furocoumarins 8-methoxypsoralen and 5-methoxypsoralen. Beside light-induced phototoxic reactions due to the photosensitizing activity of psoralens, side-effects after the oral intake of psoralens are nausea and vomiting, headaches, anxiety and sleeplessness. We report a rare case of anaphylaxis to 5-methoxypsoralen that developed during prophylactic 'hardening' therapy in a 36-year-old woman suffering from polymorphic light eruption. Anaphylaxis to 5-methoxypsoralen was established by placebo-controlled oral provocation tests.