Radioiodinated zinc phthalocyanine including [125I]ZnPcI4 and differently sulfonated [65Zn]ZnPcS (ZnPcS4, ZnPcS3, ZnPcS2 and ZnPcS1.75, a mixture of adjacent di and 25% mono) were prepared in order to study cell uptake and release kinetics in EMT-6 cells. The same compounds were evaluated for their in vitro phototoxicity and the biological parameters were compared to partition coefficients to arrive at quantitative structure-activity relationships (QSAR). At 1 microM in 1% serum, at 37 degrees C, all dyes showed rapid cell uptake during the first hour followed by a slow accumulation phase. After 24 h, the highest cellular concentration was observed with the lipophilic ZnPcI4, followed by the amphiphilic ZnPcS2 and ZnPcS1.75. The hydrophilic ZnPcS4 and ZnPcS3 showed lower uptake. Dye release from dye-loaded cells during incubation in dye-free medium could reach up to 60% and was shown to depend mainly on the amount of drug incorporated rather than the type of compound. These results suggest that care should be taken in interpreting dye toxicity data, which involve in vitro cell manipulations in dye-free medium, particularly during in vitro-in vivo protocols. The EMT-6 cell survival after 1 h or 24 h incubation with 1 microM dye in 1% serum followed by exposure to red light was assessed by means of the colorimetric 3-(4,5-dimethylthiazol-2-yl)-diphenyl-tetrazolium bromide (MTT) assay. Photocytotoxicities correlated inversely with the tendencies of the dyes to aggregate. Increased dye uptake by the cells also correlated with their activities, except for the lipophilic ZnPcI4, which showed the highest cell uptake but little phototoxicity. The QSAR between phototoxicity and the log of the partition coefficients (phosphate-buffered saline and n-octanol) gave a parabola with optimal partition values corresponding to the adjacent sulfonated ZnPcS2.

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We report thrombocytopenia and large platelets in 34 patients with 22q11.2 deletion syndrome. Our report demonstrates the absence of correlation between platelet abnormalities and other phenotypic features such as conotruncal cardiac anomalies or immunodeficiency.The 22q11.2 deletion syndrome includes a wide spectrum of clinical anomalies, among which are dysmorphic facies, velopharyngeal insufficiency with or without an overt cleft, speech delay, hypoparathyroidism, conotruncal cardiac anomalies and immunodeficiency. In this prospective study, we analysed, over a period of 4 years, platelet parameters, cardiac anomalies and immunological features in 34 patients with a 22q11.2 deletion (median age: 5 years, age range: 1 month-24 years, 25F/9M).Platelet counts (H2 Technicon, Bayer) indicated thrombocytopenia (platelet count <150·10 9 /l) in 35% (13/34) of the patients and large platelets (mean platelet volume, MPV >10 fl and median MPV 10.6 fl) were found in 82% (28/34). A strong negative correlation between MPV and platelet count was noted (correlation coefficient = À0.78). These platelet findings were not associated with bleeding tendencies, even during heart surgery.

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We report on a male patient affected by Shwachman Diamond syndrome (SDS) who presented an unusual delayed neutropenia and then developed a poorly differentiated acute myeloid leukaemia (M0-AML) with trilineage myelodysplasia in adulthood. Conventional cytogenetics revealed complex karyotypic changes (monosomies 20, 21, 22, additional 15p). The patient was treated with conventional chemotherapy but never reached complete remission of leukaemia and died 18 months after diagnosis. SDS is an inherited bone marrow failure syndrome with a high propensity to leukaemic transformation. Since neutropenia may be intermittent or with delayed onset, and leukaemic transformation may not occur until adulthood, full blood count should be regularly monitored in such patients.