Effect of alpha-difluoromethylornithine on rectal mucosal levels of polyamines in a randomized, double-blinded trial for colon cancer prevention

BACKGROUND: Polyamines (e.g., putrescine, spermidine, and spermine) are required for optimal cell growth. Inhibition of polyamine synthesis suppresses carcinogen-induced epithelial cancers, including colon cancer, in animal models. In a short-term phase IIa trial, we determined that low doses of alpha-difluoromethylornithine (DFMO), an inhibitor of ornithine decarboxylase (an enzyme involved in polyamine synthesis), reduced the polyamine content of normal-appearing rectal mucosa of subjects with a prior history of resected colon polyps. In a follow-up study, we have attempted to determine the lowest dose of DFMO that can suppress the polyamine content of rectal mucosa over a course of 1 year with no or minimal side effects. METHODS: Participants were randomly assigned to daily oral treatment with a placebo or one of three doses (0.075, 0.20, or 0.40 g/m2) of DFMO. Baseline and serial determinations of polyamine levels in rectal mucosa and extensive symptom monitoring (including audiometric measurements, since DFMO causes some reversible hearing loss at higher doses) were performed over a 15-month period. RESULTS: DFMO treatment reduced putrescine levels in a dose-dependent manner. Following 6 months of treatment, doses of 0.20 and 0.40 g/m2 per day reduced putrescine levels to approximately 34% and 10%, respectively, of those observed in the placebo group. Smaller decreases were seen in spermidine levels and spermidine:spermine ratios. Polyamine levels increased toward baseline values after discontinuation of DFMO. Although there were no statistically significant differences among the dose groups with respect to clinically important shifts in audiometric thresholds and nonaudiologic side effects, statistically significant higher dropout and discontinuation rates were observed in the highest dose group. CONCLUSIONS: Polyamine levels in rectal mucosa can be continuously suppressed by daily oral doses of DFMO that produce few or no side effects. A dose of 0.20 g/m2 can be used safely in combination phase IIb or single-agent phase III chemoprevention trials.     

Living and working overseas: School psychologists in American international schools.

Discusses American international schools and work activities for school psychologists overseas. Practical information is presented on how to secure employment overseas through placement agencies. The pressures and advantages of living overseas, within the context of work conditions and personal characteristics, are reviewed for school psychologists in the US. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Development toward an all-silicon integrated thermal management system: the integrated MCM

A new all-silicon multichip module with integrated thermal management system is presented. Our new packaging approach combines the benefits of wafer-scale integration with the flexibility of independently fabricated and pre-tested devices, allowing the development of highly integrated systems. Wet anisotropic etching is used for the dicing of silicon integrated circuits as well as for the fabrication of the chip-receiving cavities in the silicon substrate. The etching exposes {1 1 1} type planes in both chip and receiving surface, assuring a virtually perfect mating of the assemblage. The system is complemented with an integrated silicon heat sink, which can maintain heat fluxes in excess of 100 W/cm².     

Manufacturing pinhole arrays for X-ray source diagnostics using LIGA

 The manufacturing of pinhole arrays with diameters 10 μm up to 60 μm in 100–300 μm gold foils is described using LIGA. These structures are used to characterize the electron beam in a storage ring by means of the emitted synchrotron radiation. The source inside the bending magnet 13 at BESSY I (single bunch mode, 70 mA ring current, pinholes: ∅60 μm) is (448±40) μm in height and (768±40)μm in horizontal width. For BESSY II pinholes with ∅ 10–20 μm will be used utilizing bending magnet radiation (resolution ∼10 μm), single pinholes with 1–5 μm in diameter are dedicated to insertion device characterization (coherence). Received: 25 August 1997/Accepted: 23 October 1997     

Composite expansions on forced convection over a flat plate with an unheated starting length

The elliptic energy equation for steady, two-dimensional incompressible flow over a flat plate with an unheated starting length is analyzed using matched asymptotic expansions where the boundary layer solution has been treated as the outer expansion corresponding to the leading-edge equation as the inner expansion. It has been revealed that the linear velocity profile of flow occurs near the leading-edge of the heated part of the plate. This new technique for solving elliptic-to-parabolic equations involves stretching two different scales for two independent variables in the inner expansion. Results are applicable to the region where boundary layer theory breaks down, which is particularly interesting in microscale heat transfer.     

Experimental investigations in regard to the optimal stimulation of lecithin synthesis in the fetal lung via glucocorticoids (author''s transl)

A total of 187 sera positive for Hepatitis B surface antigen (HBSAg) were collected from blood banks and clinics representative for the various regions of Poland. 139 sera were from symptomless carriers of HBSAg, 34 sera--from patients with acute hepatitis, and 14 sera--from patients with chronic hepatitis. In the group of HBSAg carriers, subtype HBSAg/adw was found in 80,6% of cases, and sybtype HBSAg/ayw--in 19.4% of cases; in patients with acute hepatitis subtype adw was found in 82,5% of cases, and subtype ayw--in 17,5% of cases; in patients with chronic hepatitis subtype adw was found in 78,6% of cases, and subtype ayw--in 21,4% of cases.     

Exploring the Potential of Metal-Based Candidate Drugs as Modulators of the Cytoskeleton

During recent years, accumulating evidence suggested that metal-based candidate drugs are promising modulators of cytoskeletal and cytoskeleton-associated proteins. This was substantiated by the identification and validation of actin, vimentin and plectin as targets of distinct ruthenium(II)- and platinum(II)-based modulators. Despite this, structural information about molecular interaction is scarcely available. Here, we compile the scattered reports about metal-based candidate molecules that influence the cytoskeleton, its associated proteins and explore their potential to interfere in cancer-related processes, including proliferation, invasion and the epithelial-to-mesenchymal transition. Advances in this field depend crucially on determining binding sites and on gaining comprehensive insight into molecular drug-target interactions. These are key steps towards establishing yet elusive structure-activity relationships.