IL-17-driven intestinal fibrosis is inhibited by Itch-mediated ubiquitination of HIC-5.

Intestinal fibrosis is a major complication in inflammatory bowel diseases, but the regulatory mechanism that inhibits fibrosis remains unclear. Here we demonstrate that Itch-/-myofibroblasts express increased amounts of profibrotic collagen type I and α-SMA in response to IL-17. Mechanistically, we demonstrate that Itch directly binds to HIC-5 and targets it for K63-linked ubiquitination to inhibit IL-17-driven intestinal fibrosis. Reconstitution of Itch-/- myofibroblasts with wild-type Itch but not the Itch-C830A mutant normalized the expression of profibrotic genes. Similarly, shRNA-mediated inhibition of HIC-5 normalized the expression of profibrotic gene expression. Thus, we have uncovered a novel mechanism by which Itch negatively regulates intestinal fibrosis.

Resonant Electron Transfer in Collisions between Two Fullerene Ions.

Fullerenes are a direct link between atoms with discrete electronic energy levels and solids with a band structure and a well-defined surface. In this Letter, we report on the first ever experiment on resonant electron transfer in collisions between two fullerene ions. Total cross sections have been measured for the reaction C+60+C2+60-->C2+60+C+60 at center-of-mass energies ranging from 27 to 69 keV. Surprisingly, within the error bars, these cross sections are identical to the respective cross sections for C+60+C60 measured by Rohmund and Campbell [J. Phys. B 30, 5293 (1997)]]. We show that the experimental data for both collision systems are very well reproduced by a quantum mechanical treatment of the reaction based on the concept of hole particles and the polarizability of the fullerene molecule.

Hypericin activated by an incoherent light source has photodynamic effects on esophageal cancer cells.

BACKGROUND AND AIMS: Photodynamic therapy (PDT) is a new treatment modality for early esophageal neoplasia. With two absorption maxima in the visible light range (550 and 588 nm) hypericin is a very promising photosensitizer for PDT with incoherent light sources. We studied the effects of photosensitizing hypericin in both primary cell cultures and cell lines (squamous: Kyse-140 and adenocarcinoma: OE-33) of human esophageal cancer using an incoherent white light source. MATERIALS AND METHODS: Esophageal cancer cells were preincubated (4-24 h) with hypericin (10 nM-1 micro M) and then irradiated with a light energy dose of 30 J/cm(2). RESULTS: Hypericin showed strong phototoxic effects and induced apoptosis in a dose-dependent fashion. The IC(50) value of hypericin phototoxicity was approximately 30 nM in both squamous and adenocarcinoma cells. In the concentrations used nonphotoactivated hypericin showed no toxic or apoptotic potency. The phototoxicity of hypericin was compared to that of delta-aminolevulinic acid (5-ALA), which is already being used for photodynamic therapy of gastrointestinal cancer. 5-ALA produced similar phototoxic effects but at a much higher dose (IC(50) 182+/-8 micro M in Kyse-140 and 308+/-40 micro M in OE-33 cells). Moreover, 5-ALA did not induce apoptosis to a relevant extent. CONCLUSION: Hypericin is a very promising new photosensitizer for innovative photodynamic therapy of esophageal cancer. Both the well known clinical safety of hypericin and the lower costs of broad band light sources argue in favor of clinical trials.

[Comparative study of the anti-arrhythmia effect of flecainide acetate and prajmalium bitartrate in patients with tachycardiac ventricular rhythm disorders]. / Vergleichende Untersuchung über den antiarrhythmischen Effekt von Flecainidacetat und Prajmaliumbitartrat bei Patienten mit tachykarden ventrikulären Rhythmusstörungen.

In an open randomized therapeutic study, 20 patients known to have frequent ventricular premature beats (VPB) and/or ventricular pairs (VP) were treated with both 2 X 200 mg flecainide (F) and 4 X 20 mg prajmalium-bitartrate (P) for 3 months each. There was a drug-free interval of one week between the two therapy phases. 24-hour long-term ECG-registrations were carried out before the start of the therapy phases as well as 1 week, 1 month, 2 months and 3 months after the initiation of antiarrhythmic therapy. After one week, the group as a whole evidenced a VPB reduction of 94% under F and only 57% under P (p less than or equal to 0.05). The percentage of individual patients in whom there was a statistically significant VPB reduction was also higher under F than under P (65% vs. 40%). In the group as a whole, there was a VP reduction of 99% under F and 88% under P (p less than or equal to 0.05) after one week. Of the 13 individuals with frequent VP (over 16 VP/24 h), a significant reduction was seen in 77% under F and only 38% under P. The difference between the two antiarrhythmic agents registered after one week was also observed in the further course of therapy but could no longer be statistically confirmed for the ventricular pairs. An aggravation of ventricular arrhythmias was observed in 2 patients under F and in 3 under P.(ABSTRACT TRUNCATED AT 250 WORDS)

Effect of finite analyzer size on the distribution functions measured in field-free plasmas.

Ideal, gridded, planar electrostatic retarding field analyzers correctly measure isotropic velocity distributions in field-free plasmas if the grid and collector are infinite. However, the finite apertures in practical analyzers block some particles that have sufficient momentum to be collected. We calculated the resulting error in the measured distribution function for a range of analyzer sizes when a Maxwellian distribution enters the analyzer.