Improved 32P-postlabelling assay for the quantification of the major platinum-DNA adducts

For the improvement of chemotherapy with platinum (Pt)-containing drugs a sensitive assay to detect the induced Pt-DNA adducts is needed. Therefore, the 32P-postlabelling assay, described by Blommaert and Saris (Nucleic Acids Res., 1995, 23, 1300-1306), to detect the major adducts Pt-GG and Pt-AG has substantially been improved and compared with ELISA and AAS. For the quantification of the adducts, TpT was added as an internal standard immediately after isolation of the Pt- adducts from digested DNA samples. It was found that 32P-labelling of both GpG and ApG, the dinucleotides obtained after deplatination of the adducts, was equally efficient as that of TpT. To isolate the Pt- adducts on basis of a positive charge, the pH of DNA digests was adjusted to approximately 3 prior to separation by strong cation- exchange chromatography. For the subsequent deplatination a volume of only 12 microl of 0.2 M NaCN was used, which did not interfere with the following labelling step. The quantification of the 32P-labelled dinucleotides was performed by phosphorimaging of spots after separation on TLC as well as by 32P-counting of fractions collected after separation by HPLC. The method was used to determine adduct levels in in vitro cisplatin-treated DNA and in DNA isolated from cisplatin-treated cultured cells, tumor xenografts from cisplatin- treated mice, and from white blood cells and (tumor) tissues from cisplatin-treated patients. The results show a significant correlation with the adduct levels as determined with atomic absorption spectroscopy (high levels) or with specific antibodies (low levels). This assay appears to be useful for the determination of low levels of Pt-adducts in small DNA samples as present in clinical specimens such as blood and tumor tissue, but also in buccal mucosal cells and fine needle aspirates.      

The natural history of hidradenitis suppurativa

AIM: To investigate aspects of the natural history of hidradenitis. BACKGROUND: The natural history of hidradenitis suppurativa (HS) is not well known. There is incomplete published data on the average age of disease onset, progression of the disease, average monthly incidence and duration of boils, and factors that relieve or exacerbate disease symptoms. STUDY DESIGN: Questionnaire-based survey among HS patients identified from hospital records of three hospitals in Nottinghamshire, UK. RESULTS: One hundred and ten of 156 questionnaires (70.5%) were returned, 93 from females and 17 from males. The average patient's age was 40.1 years and the average reported age of disease onset was 21.8 years. At the time of the survey patients had suffered an average disease duration of 18.8 years. Most patients (98 of 110) still had experienced active disease within the past year. There was some evidence that in women the condition has a tendency to ease or subside after the menopause. Forty-four per cent of women felt that their condition was aggravated by menstruation. Thirty-eight per cent of patients gave a positive family history of the disorder. The average duration of painful boils was 6.9 days. In addition, 62% of patients acknowledged the presence of permanently painful boils that failed to subside. Patients developed a median of two boils per month. Factors that could aggravate the condition were primarily sweating or heat, stress or fatigue and tight clothing or friction. Factors that could improve the condition consisted largely of a variety of medical treatments and a number of life-style measures, such as swimming or baths. Twenty-four per cent of patients had failed to find anything at all to help their condition, despite an average disease duration of almost 19 years. CONCLUSIONS: The study highlights several of the factors that make HS one of the most distressing dermatological diseases, such as the average monthly incidence of painful lesions, their average duration and the chronicity of the disease. It seems striking that the mean duration of an HS boil (6.9 days) roughly equals the duration of an average course of antibiotics. The postulated response of HS to oral antibiotics may thus simply have its explanation in the natural history of the condition itself.     

Paediatric psoriasis – narrowband UVB treatment

Narrowband UV‐B is a safe and efficacious option for the treatment of adult psoriasis. However, the use of this therapy has been limited in children due to its long‐term carcinogenic potential. It has proven to be an adequate alternative in patients whose condition is refractory to topical treatment. Aims To evaluate the efficacy and short‐term safety of narrowband UV‐B in the treatment of paediatric psoriasis, and to compare our results with those obtained in other studies on paediatric psoriasis. Materials and methods Over a period of 2 years and 4 months, we administered narrowband UV‐B to 20 children diagnosed with psoriasis that was refractory to topical therapy. The therapeutic response was measured using the Psoriasis Area and Severity Index (PASI). Results Between August 2005 and December 2007, 20 children received narrowband UV‐B. Their median age was 13 years (range, 5–17 years), and the median initial PASI score was 8.25 (2.7–22.2). A median of 28 (10–59) sessions was required to achieve clearance, reaching almost complete or total remission (median final PASI) in all but two patients. Six patients required a new therapeutic course because of relapse, and the mean duration of remission was 8 months (4–18). No patients experienced severe adverse events during therapy, and only one discontinued treatment, for unrelated reasons. Discussion and conclusion Narrowband UV‐B for the treatment of paediatric psoriasis has received little attention in the literature. This treatment has been limited in children because of its potential long‐term carcinogenic effects, and most information has been extrapolated from adults. Nevertheless, narrowband UV‐B phototherapy is an effective and well‐tolerated therapeutic alternative in paediatric patients with severe psoriasis.     

Rising trends in incidence of cutaneous malignant melanoma and their future projections in Catalonia,Spain: increasing impact or future epidemic?

Background During the past decades, there has been a substantial increase in the incidence of cutaneous malignant melanoma (CMM) among all Caucasian populations. Spain presents one of Europe’s lowest incidence and mortality rates. Objective The aim of this study was to analyse the recent trends of CMM incidence and mortality in a region with lower incidence as well as to project their future trends. Methods Cutaneous malignant melanoma incidence data were provided by the Tarragona and Girona population‐based cancer registries and mortality data were provided by the Mortality Registry of Catalonia. Time trends of incidence and mortality rates by CMM were assessed through the estimated annual percentages of change of the incidence and mortality age‐standardized rates to the World Standard Population. Projections were based on a Bayesian age–period–cohort model using second order autoregressive effects on age. Results During the last 20 years CMM incidence has increased substantially at a faster rate than any other neoplasms in Catalonia, particularly among women and this trend will probably continue for the next several years. Nevertheless, CMM mortality trends have been and probably will remain stable during this period. Conclusion Improvements in preventive activities should be implemented to decrease incidence and mortality from this cancer. Monitoring stage‐specific trends in CMM incidence can assess the impact of preventive strategies; for this reason more complete information on diagnostic features of CMM patients in the Spanish population‐based cancer registries are necessary.     

甘草叶中黄酮类成分的化学研究

自甘草(Glycyrrhiza uralensis Fisch)的叶中分离到四个黄酮类化合物。根据理化性质,光谱(UV,MS,¹HNMR)数据分析,分别确定结构为3,5,7,3′,4′-五羟基-5′-异戊烯基黄酮(Ⅰ),3,6,7,3′,4′-五羟基-2′-异戊烯基黄酮(Ⅱ),5,7,3′,4′-四羟基-5′-异戊烯基二氢黄酮(Ⅲ)和槲皮素-3,3′-二甲醚(Ⅳ)。其中,Ⅰ,Ⅱ和Ⅲ是新化合物,分别命名为乌拉尔醇(uralenol),新乌拉尔醇(neouralenol)和乌拉尔宁(uralenin)。Ⅳ在本属植物中为首次发现。Ⅲ为甘草叶中的主要黄酮类成分。本文解释了B环某些裂解碎片丰度与异戊烯基和氧取代基相对位置的关系。