Expression and Function of Macrophage Migration Inhibitory Factor in the Pathogenesis of UV-Induced Cutaneous Nonmelanoma Skin Cancer(†)

Chronic skin exposure to ultraviolet light stimulates the production of cytokines known to be involved in the initiation of skin cancer. Recent studies in mouse models suggested a role for macrophage migration inhibitory factor (MIF) in the UVB‐induced pathogenesis of nonmelanoma skin cancer (NMSC). Our studies aimed at defining the pathophysiological function of MIF in cutaneous inflammatory reactions and in the development and progression of NMSC. Immunohistochemical analysis revealed a moderate expression of MIF in normal human skin samples but an enhanced expression of this cytokine in lesional skin of patients with actinic keratosis or cutaneous SCC. Enzyme‐linked immunosorbent assay studies showed a time‐dependent increase in MIF secretion after a moderate single‐dose UVB irradiation in NHEKs and SCC tumor cells. MIF is known to interact with CXCR2, CXCR4 and CD74. These receptors are not constitutively expressed in keratinocytes and HaCaT cells and their expression is not induced by UVB irradiation either. However, stimulation with IFNγ upregulated CD74 surface expression in these cells. Affymetrix^® Gene Chip analysis revealed that only keratinocytes prestimulated with IFNγ are responsive to MIF. These findings indicate that MIF may be an important factor in the pathogenesis of NMSC tumorigenesis and progression in an inflammatory environment.     

An efficient synthesis of novel 2,4-disubstituted tetrahydroquinolines and quinolines

A series of novel tetrahydroquinolines have been synthesized via the acid-catalyzed reaction of an azaflavan-4-ol with a variety of reactive nucleophiles. The tetrahydroquinolines were found to undergo oxidation in the presence of iodine as catalyst to generate the corresponding novel 2,4-disubstituted quinolines.     

The effect of an additional reflection in a precedence effect experiment

Studies on the precedence effect typically utilize a two-source paradigm, which is not realistic relative to real world situations where multiple reflections exist. A step closer to multiple-reflection situations was studied using a three-source paradigm. Discrimination of interaural time differences (ITDs) was measured for one-, two-, and three-source stimuli, using clicks presented over headphones. The ITD was varied in either the first, second, or the third source. The inter-source intervals ranged from 0-130 ms. A perceptual weighting model was extended to incorporate the three-source stimuli and used to interpret the data. The effect of adding a third source could mostly, but not entirely, be understood by the interaction of effects observed in the precedence effect with two sources. Specifically, for delays between 1 and 8 ms, the ITD information of prior sources was typically weighted more heavily than subsequent sources. For delays greater than 8 ms, subsequent sources were typically weighted slightly more heavily than prior sources. However, there were specific conditions that showed a more complex interaction between the sources. These findings suggest that the two-source paradigm provides a strong basis for understanding how the auditory system processes reflections in spatial hearing tasks.     

Droplet relaxation in blends with one viscoelastic component: bulk and confined conditions

Using a counter rotating parallel plate shear flow cell, the shape relaxation of deformed droplets in a quiescent matrix is studied microscopically. Both the effects of geometrical confinement and component viscoelasticity are systematically explored at viscosity ratios of 0.45 and 1.5. The flow conditions are varied from a rather low to a nearly critical Ca number. Under all conditions investigated, viscoelasticity of the droplet phase has no influence on shape relaxation, whereas matrix viscoelasticity and geometrical confinement result in a slower droplet retraction. Up to high confinement ratios, the relaxation curves for ellipsoidal droplets can be superposed onto a master curve. Confined droplets with a sigmoidal shape relax in two stages: the first consists of a shape change to an ellipsoid with a limited amount of retraction, and the second is the retraction of this ellipsoid. The latter stage can be described by means of one single relaxation time that can be obtained from the relaxation of initially ellipsoidal droplets. The experimental results are compared to the predictions of a recently published phenomenological model for droplet dynamics in confined systems with viscoelastic components (Minale et al., Langmuir 26:126–132, 2010). However, whereas the model predicts additive effects of geometrical confinement and component viscoelasticity, the experimental data reveal more complex interactions.     

Ionic conductivity and battery characteristic studies on PEO+NaClO3 polymer electrolyte

Solid polymer electrolyte films based on poly (ethylene oxide) PEO complexed with NaClO₃ have been prepared by a solution-cast technique. The solvation of Na⁺ ion with PEO is confirmed by XRD and IR studies. Measurements of the a.c. conductivity in the temperature range 308 – 378 K and the transference numbers have been carried out to investigate the charge transport in this polymer electrolyte system. Transport number data show that the charge transport in this polymer electrolyte system is predominantly due to ions. The highest conductivity (2.12.10⁻⁴ S/cm) has been observed for the 70:30 composition. Using the polymer electrolyte solid state electrochemical cells have been fabricated. The various cell parameters are evaluated and reported.     

Physical and Chemical Characterization of Therapeutic Iron Containing Materials: A Study of Several Superparamagnetic Drug Formulations with the β-FeOOH or Ferrihydrite Structure

The effectiveness of therapeutically used iron compounds is related to their physical and chemical properties. Four different iron compounds used in oral, intravenous, and intramuscular therapy have been examined by X-ray powder diffraction, iron-57 Mössbauer spectroscopy, transmission electron microscopy, BET surface area measurement, potentiometric titration and studied through dissolution kinetics determinations using acid, reducing and chelating agents. All compounds are nanosized with particle diameters, as determined by X-ray diffraction, ranging from 1 to 4.1 nm. The superparamagnetic blocking temperatures, as determined by Mössbauer spectroscopy, indicate that the relative diameters of the aggregates range from 2.5 to 4.1 nm. Three of the iron compounds have an akaganeite-like structure, whereas one has a ferrihydrite-like structure. As powders the particles form large and dense aggregates which have a very low surface area on the order of 1 m²?g^?1. There is evidence, however, that in a colloidal solution the surface area is increased by two to three orders of magnitude, presumably as a result of the break up of the aggregates. Iron release kinetics by acid, chelating and reducing agents reflect the high surface area, the size and crystallinity of the particles, and the presence of the protective carbohydrate layer coating the iron compound. Within a physiologically relevant time period, the iron release produced by acid or large chelating ligands is small. In contrast, iron is rapidly mobilized by small organic chelating agents, such as oxalate, or by chelate-forming reductants, such as thioglycolate.