Synthese und Pharmakodynamische Aktivität von 2-(3-(2-Phenylethyl)benzofuran-2-yl)-N-propyl-ethanamin

Synthesis and Pharmacodynamic Activity of 2-(3-(2-Phenylethyl)benzofuran-2-yl)-N-propyl-ethanamine The benzofuranethanamines 3a and 3b were synthesized and pharmacologically tested to investigate structure-activity relationships with antiarrhythmic compounds. The key-step in the synthesis was the chemoselective reduction of the chloroacetyl-dihydrobenzofurane 5 to chloroethylbenzofurane 9 using triethylsilane/BF₃ ? Et₂O. Results of a series of further attempts to reduce 5 are also described. Pharmacological investigations on isolated guinea pig heart muscle preparations showed that 3a exhibits similar negative inotropic and negative chronotropic action in comparison to propafenone and the conformationally restricted benzofurane 1a . In contrast to these substances, however, 3a shows no β₁-adrenozeptor blocking activity.     

Radiology department management system: technologists' costs

We developed a series of management reports to compare actual costs against expected costs for radiology departments on a more detailed level than previously available. We first developed labor standards for the most commonly employed diagnostic examinations and showed that increased patient complexity (resulting from, for example, immobility, precautions status, etc.) also increased the examination times up to 2.6-fold compared with the time required for average patients. Using labor standards and budgeted and actual volumes of average and complex patients, we calculated four types of variances: volume variance, examination mix variance, patient complexity variance, and technologist efficiency variance. Monitoring the technologist efficiency variance over time could be one key piece of information for improving departmental productivity.     

NMR fragment screening: tackling protein-protein interaction targets

High-throughput screening of libraries containing compounds of 'drug-like' molecular weight has frequently resulted in no or poor drug candidates, especially when screening against demanding drug targets such as protein-protein interactions. Fragment-based lead discovery and optimization has evolved as a promising solution to this problem by combining the universal adaptability of low-molecular-weight fragments with immediate structural information on fragment binding modes. This review focuses on nuclear magnetic resonance (NMR) fragment screening techniques, which provide a unique combination of medium-throughput, direct binding site information and broad applicability. The utility and exemplary data of chemical shift-detected NMR fragment screening applied to the challenging protein-protein interaction target PDZ domains are summarized.     

Liver transplantation for hepatitis B in the United States

AIM: To evaluate the impact of hepatitis B virus (HBV) on US health care system, we reviewed the Organ Procurement and Transplantation (OPTN, formerly UNOS) HBV database. METHOD: We reviewed records of liver transplantations (LTx) performed in the United States listed for the diagnoses of HBV between 1993 and mid-October 2004. Both acute as well as chronic cases were included. Coinfection with hepatitis C virus was excluded from study. The specific states selected for review were chosen from those areas that are receiving large numbers of new immigrants from high HBV endemic areas (ie, Texas, Pennsylvania, California, New York, and Florida). One-, 3-, and 5-year patient survival rates for both cadaveric and living related donors were analyzed. Survival rates were obtained from OPTN database as Kaplan-Meyer survival test. RESULTS: Between 1993 and mid-October 2004, 53,312 LTx had been performed nationwide. Of these, 2314 (4.34%) were performed for the diagnosis of HBV; 1816 cases (78%) were due to chronic HBV infection (45 of them were living donor LTx) and 498 cases (22%) were due to HBV-induced acute liver failure (seven of them were living donor LTx). Three- and 5-year survival rates of chronic HBV-related LTx patients were better than acute HBV-related and overall LTx patients. CONCLUSION: HBV is generally considered to have a minor health significance by many community gastroenterologists. With growing immigration from overseas, it may eventually have a higher impact on LTx. Therefore, it is crucial to further educate gastroenterologists and primary care physicians caring for this specific group of patients.     

The relation between deoxycytidine kinase activity and the radiosensitising effect of gemcitabine in eight different human tumour cell lines

Background  

Gemcitabine (dFdC) is an active antitumour agent with radiosensitising properties, shown both in preclinical and clinical studies. In the present study, the relation between deoxycytidine kinase (dCK) activity and the radiosensitising effect of gemcitabine was investigated in eight different human tumour cell lines.     

TUCAN/CARDINAL/CARD8 and apoptosis resistance in non-small cell lung cancer cells

Background  

Activation of caspase-9 in response to treatment with cytotoxic drugs is inhibited in NSCLC cells, which may contribute to the clinical resistance to chemotherapy shown in this type of tumor. The aim of the present study was to investigate the mechanism of caspase-9 inhibition, with a focus on a possible role of TUCAN as caspase-9 inhibitor and a determinant of chemosensitivity in NSCLC cells.