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Background Transfusion-related morbidity is an emerging problem in chronically transfused patients with myelodysplastic syndromes (MDS). Although several iron-chelating drugs are available, the optimal way of treatment of iron-overload remains uncertain. A major disadvantage of deferoxamine is that the drug has to be applied as continuous subcutaneous infusion. Therefore, novel oral agents have been developed. One of these drugs is deferasirox (Exjade®). Materials and methods We report on 14 MDS patients who were treated with deferasirox (500–1500 mg daily) for up to 24 months. In these patients, treatment responses were recorded by determining serum ferritin levels before and during therapy and by applying recently established response criteria. Results In all patients except one, ferritin levels decreased during therapy. Four patients showed a complete response, one a minor response and five a stable iron load. In the responding patients, initially elevated liver enzymes decreased substantially. No substantial change in transferrin saturation or transfusion frequency was recorded. Side effects were mild and tolerable in most patients. In one patient, treatment with deferasirox was stopped because of impaired kidney function. Conclusion Our data show that treatment with deferasirox is a reasonable approach to counteract iron overload in patients with MDS.

Cytotoxic hydroxyethyl-substituted (amine)platinum(II) and -(IV) complexes have recently attracted attention because of the ability of their hydroxyethyl groups to coordinate through the oxygen atom to the platinum centre during oxidation with hydrogen peroxide or through intramolecular ligand exchange reactions in dichloroplatinum(II) complexes. The last point in particular is of great interest, because the intramolecular attack of the hydroxy group dramatically influences the mode of action of platinum(II) compounds. On the other hand, there is also the chance to use such reactions specifically for the synthesis of novel anticancer platinum-based drugs for chemotherapy. We have therefore focused our chemistry program on the synthesis of dichloroplatinum(II) complexes that are in a position to form singly and, especially, doubly ring-closed alcoholato species and on investigation of their structures by X-ray crystallography. It was possible to determine the crystal structures of [Pt{(R)-(−)-HL}2Cl2], [Pt{(S)-(+)-HL}2Cl2], [Pt{(R)-(−)-HL}{(S)-(+)-HL}Cl2], [Pt{(S)-(+)-HL}{(S)-(+)-L}Cl], [Pt{(R)-(−)-L}2] and [Pt{(S)-(+)-L}2] (HL = 2-aminobutanol-κN, L = 2-aminobutanolato-κ2N,O). The results obtained may represent the first step towards novel prodrugs for platinum-based antitumour chemotherapy. (© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2003)

Capillary electrophoresis (CE) was used as an assay for studying the interaction of (SP-4-2)-bis[(R)-(-)-2-aminobutanol)dichloroplatinum(II) (1) and (SP-4-2)bis(4-aminobutanol)dichloroplatinum(II) (2) with guanosine 5'-monophosphate (GMP). CE kinetic measurements carried out at two physiological pH levels indicated that upon increasing the pH, 1 showed an appreciable change in binding behavior, with the rate of binding increased for more than 10 times as expressed by apparent half-life values of GMP (6.1 and 62.2 h at pH 6.0 and 7.4, respectively). The rate of GMP binding for 2 remained comparatively less affected by pH (half-lives of 8.5 and 10.6 h, respectively). Regardless of the nature of platinum complex and pH, the reaction with GMP tends to be decelerated at increased chloride concentrations in solution, this effect being particularly pronounced when changing from 4 mM (intracellular level) to 100 mM (extracellular level). The kinetic differences of platinum complexes were characterized in terms of the respective GMP-adducts structure, independently identified by means of off-line electrospray ionization-mass spectrometry. Also addressed was the interpretation of binding behavior as based on the structural features of the intact complexes, namely differing inclination to intramolecular chelation.

The present study has focused on a general reaction procedure for the derivatization of hydroxyethyl-substituted tetrachloro(ethane-1,2-diamine)platinum(IV) compounds at peripheral hydroxyl groups using acyl chlorides. A new class of platinum(IV) complexes could be synthesized which now opens the possibility for the first time to couple the cytotoxic platinum(IV) moiety to carrier molecules like proteins and antibodies in a very selective way. Moreover, it is now possible to synthesize platinum(IV) complexes with ligands in the equatorial plane which are not very stable in the presence of oxidizing agents.

The bis(ethanolamine)platinum complexes (SP-4-2)-dichlorobis(2-hydroxyethylamine)platinum(II) (1) and (OC-6-22)-tetrachlororbis(2-hydroxyethylamine)platinum(IV) (2) have been synthesized and their chemistry in aqueous solution has been investigated due to the fact that 1 forms very stable monoadducts with 5′-GMP. In water 1 and 2 are converted into (SP-4-3)-chloro(2-ethanolatoamine-κ2N,O)(2-hydroxyethylamine)platinum(II) (3) and (OC-6-31)-trichloro(2-ethanolatoamine-κ2N,O)(2-hydroxyethylamine)platinum(IV) (4) with a chelating ethanolatoamine ligand by a intramolecular ligand exchange reaction, which was confirmed by 1H and 2D 15N,1H-HMQC NMR experiments and the crystal structure determination of 4.

Restoration concepts for large river systems are currently in an early stage of development. Possibilities for, and constraints of, rehabilitation—both from a process-oriented view as well as from the nature conservation perspective—differ strongly according to the degree of anthropogenic changes. This requires precisely formulated amelioration goals. Well-conceived and thoroughly analysed case studies are necessary to better understand reversibility, direction and time scale of changes, and the sustainability of various scenarios. It is important to plan controllable set-ups with long-term monitoring in the pre- and post-implementation phases of restoration programmes. In order to achieve these goals, monitoring instruments have to be developed and calibrated that allow the definition and analysis of improvements. Finally, controlled restoration programmes offer the opportunity for large-scale experiments to test overall concepts and hypotheses and have an important heuristic value to improve the understanding of river ecology in general. Copyright © 1999 John Wiley & Sons, Ltd.

Zwar erwünscht, aber doch überraschend, waren die Ergebnisse, die wir jetzt mit Phosgen und Diphosgen als "Acylierungsmittel" in dieser Zersetzungsreaktion fanden. Als Reaktionsprodukte wurden in sehr guten Ausbeuten die 2-Isocyanato-2-alkensäureester 2 erhalten.

Amino Acids, 18. – Preparation and Reactions of 2-Isocyanato-2-alkenoates 2-Isocyanato-2-alkenoates 3 were obtained in good yields by the perrhenate-catalyzed decomposition of 2-azidoalkanoates 1 in the presence of diphosgene (2a) or phosgene (2b). Methyl 2-azidopropionate (1h) reacts to give a mixture of methyl 2-isocyanato-2-propenoate (3h) and methyl 2-chloro-2-isocyanatopropionate (4). The addition product 4 could easily be converted into 3h by elimination of HCl with triethylamine at 0°C. With benzyl alcohol (5a) and tert-butyl alcohol (5b) the isocyanates 3 react smoothly to give the corresponding Z- or Boc-protected 2,3-didehydroamino acid esters 6 and 7, respectively. The acrylic acid derivative 3h reacts as dienophile with various dienes to yield the Diels-Alder adducts 8–10.

BACKGROUND: Lineage involvement and maturation arrest are considered to have prognostic significance in patients with myelodysplastic syndromes (MDS). However, although the prognostic value of neutropenia, thrombocytopenia, and monocytosis have been documented, little is known about the impact of eosinophils and basophils. METHODS: The authors examined the prognostic significance of eosinophils and basophils in 1008 patients with de novo MDS. Patients were enrolled from 3 centers of the Austrian-German MDS Working Group and were analyzed retrospectively. Blood eosinophils and basophils were quantified by light microscopy, and their impact on survival and leukemia-free survival was calculated by using Cox regression. RESULTS: Eosinophilia (eosinophils >350/μL) and basophilia (basophils >250/μL) predicted a significantly reduced survival (P < .05) without having a significant impact on leukemia-free survival. In multivariate analysis, eosinophilia and basophilia were identified as lactate dehydrogenase (LDH)-independent prognostic variables with International Prognostic Scoring System (IPSS)-specific impact. Although elevated LDH was identified as a major prognostic determinant in IPSS low-risk, intermediate-1 risk, and high-risk subgroups, the condition “eosinophilia and/or basophilia” was identified as a superior prognostic indicator in the IPSS intermediate-2 risk subgroup. CONCLUSIONS: The evaluation of eosinophils and basophils in patients with MDS was helpful and may complement the spectrum of variables to optimize prognostication in MDS. Cancer 2010. © 2010 American Cancer Society.