An increase in the number of patients with end stage heart failure is leading to increased use of ventricular assist devices (VAD). However, sometimes the optimal time point for implantation of left ventricular or biventricular support remains unclear. Data analysis using an electronic database may help to make the decision making process more precise and thus improve outcome. However, it is not easy to find a balance between sufficient comprehensiveness of the data, which are selected from a huge amount of available information, and practicability of database maintenance and data analysis.We developed the Assist Database based on Access for Windows. The Assist Database consists of five main parts: (1) demographic and admission data, diagnosis, goal, and type of VAD; (2) preoperative period; (3) postoperative period up to 30 days; (4) follow-up period; and (5) statistical evaluation. The preoperative and postoperative parts include hemodynamic data; ventilatory support; laboratory results; results from echocardiographic, neurologic, pathologic, and other examinations; medication; and complications. The follow-up part documents readmissions, complications, and outcome.From April 1987 to October 2002, eight different types of VAD were implanted in 654 patients in our institution. Their data were retrospectively added to the Assist Database using medical records and different previously used electronic databases. Since the Assist Database came into routine use, it has been supplied daily with selected data of current patients. On the data entry level, the data arising from medical records are entered either manually via standard forms or automatically from other electronic documentation systems used in our hospital in routine patient care to collect laboratory results, demographic data, blood transfusion data, and operative data and from electronic patient charts via interfaces. The structure of the database is designed to facilitate the data analysis level.The database presented is one of three databases united to form a network. The structure of the Assist Database facilitates comprehensive, time saving data collection, which allows different online data analyses. These analyses may affect the decision making process and thus improve outcome. However, achieving a balance between the volume of available information, the time consumed, and the relevance of the data for further analysis remains difficult. The Assist Database should include information relevant for the decision making process and for the prediction of outcome. In particular, data collection should be focused on patients' preoperative condition and on postoperative organ function and quality of life. Further, different databases (for patients with congestive heart failure, assist device patients, and transplanted patients) should be unified to form a network to avoid the repeated collection of identical data, to save time, and to increase the quality of analysis. In the long term, multicenter use of the Assist Database could be considered.

The determination of histone deacetylase (HDAC) activity and the screening of potential inhibitors is gaining increasing importance due to the involvement of HDAC in transcription regulation. The level of histone acetylation can be modulated by HDAC inhibitors resulting in differentiation and/or apoptosis in cancer cells. We have previously reported the development of a nonisotopic assay for HDAC using a fluorescent derivative of epsilon -acetyl lysine. Here we report fluorescein-labeled octapeptides which are substrates for HDAC that bear closer resemblance to the native substrate. HPLC with fluorescence detection is successfully applied to the analysis of the time- and site-dependent deacetylation. LC-MS analyses are used to confirm the findings. The observed selectivity toward one of two possible deacetylation sites might result from steric hindrance by the label but the methodology presented here could be applied to similar larger peptides which might be improved tools to characterize HDAC site selectivity in vitro.

The determination of the activity of histone deacetylase (HDAC) and the potency of its inhibitors has become an important goal in medicinal chemistry. This is due both to the involvement of HDAC in gene regulation and the ability of its inhibitors to modulate transcription and induce differentation and/or apoptosis in cancer cells. We have previously reported the development of a non-isotopic assay for HDAC using a fluorescent derivative of ε-acetyl lysine. It can replace existing methods that rely on radioactively labeled histones or oligopeptides as substrates. Here we report validation and improvement of the procedure using an internal standard for the quantitation of the fluorescent substrate by HPLC.

Inhibitors of histone deacetylase (HD) are of great potential as new drugs due to their ability to influence transcriptional regulation and to induce apoptosis or differentiation in cancer cells. So far only radioactive enzyme activity assays or in vivo assays with subsequent electrophoresis and immunoblotting existed to study the activity of HD and potential inhibitors. To aid in the search of new inhibitors, a non-radioactive screening assay was sought and we have previously succeeded in establishing this for the first time. The assay uses an aminocoumarin derivative of an Omega-acetylated lysine as substrate for the enzyme. Here we report full experimental details, the evaluation of other potential substrates, and comparative analysis of various inhibitors. This advantageous method should have an impact on further developments in the field.

Inhibitors of histone deacetylase (HD) bear great potential as new drugs due to their ability to modulate transcription and to induce apoptosis or differentiation in cancer cells. To study the activity of HD and the effect of potential inhibitors in vitro so far only radio-active assays have existed. For the search of new inhibitors and for the use in HD identification and purification we established a simple, non-radioactive assay that allows screening of large numbers of compounds. The assay is based on an aminocoumarin derivative of an Omega-acetylated lysine as enzyme substrate.

Inhibitors of histone deacetylase are potent inducers of differentiation and bear considerable potential as drugs for chemoprevention and treatment of cancer. So far only complex natural products and a few synthetic congeners have been identified as specific inhibitors. We have prepared a set of simple analogues in as little as four synthetic steps that have inhibitory potencies in the range of known cyclotetrapeptide inhibitors. These compounds are interesting leads for the design of potent inhibitors of histone deacetylase.

Das Absorptionsmaximum von Proteinen im Infrarot-Licht bei 6//m entspricht dem Absorptionsminimum von Cellulose-Acetat. Es läßt sich daher ungefärbtes Protein auf Cellulose-Acetat-Folie im Bereich von 10—300 g quantitativ bestimmen. Wegen der geringen Streuung im Infrarot im Vergleich zu sichtbaren Licht ist es nicht nötig, die Folie transparent zu machen. Es ist somit prinzipiell möglich, die Auswertung von Serum-Elektropherogrammen auf Cellulose-Acetat-Folie erheblich zu vereinfachen.