Photodynamic and Nail Penetration Enhancing Effects of Novel Multifunctional Photosensitizers Designed for The Treatment of Onychomycosis

Novel multifunctional photosensitizers (MFPSs), 5,10,15‐tris(4‐N‐methylpyridinium)‐20‐(4‐phenylthio)‐[21H,23H]‐porphine trichloride (PORTH) and 5,10,15‐tris(4‐N‐methylpyridinium)‐20‐(4‐(butyramido‐methylcysteinyl)‐hydroxyphenyl)‐[21H,23H]‐porphine trichloride (PORTHE), derived from 5,10,15‐Tris(4‐methylpyridinium)‐20‐phenyl‐[21H,23H]‐porphine trichloride (Sylsens B) and designed for treatment of onychomycosis were characterized and their functionality evaluated. MFPSs should function as nail penetration enhancer and as photosensitizer for photodynamic treatment (PDT) of onychomycosis. Spectrophotometry was used to characterize MFPSs with and without 532 nm continuous‐wave 5 mW cm^?2 laser light (± argon/mannitol/NaN₃). Nail penetration enhancement was screened (pH 5, pH 8) using water uptake in nails and fluorescence microscopy. PDT efficacy was tested (pH 5, ± argon/mannitol/NaN₃) in vitro with Trichophyton mentagrophytus microconida (532 nm, 5 mW cm^?2). A light‐dependent absorbance decrease and fluorescence increase were found, PORTH being less photostable. Argon and mannitol increased PORTH and PORTHE photostability; NaN₃ had no effect. PDT (0.6 J cm^?2, 2 μm ) showed 4.6 log kill for PORTH, 4.4 for Sylsens B and 3.2 for PORTHE (4.1 for 10 μm ). Argon increased PORTHE, but decreased PORTH PDT efficacy; NaN₃ increased PDT effect of both MFPSs whereas mannitol increased PDT effect of PORTHE only. Similar penetration enhancement effects were observed for PORTH (pH 5 and 8) and PORTHE (pH 8). PORTHE is more photostable, effective under low oxygen conditions and thus realistic candidate for onychomycosis PDT.     

Method to quantitate absorption coefficients from single fiber reflectance spectra without knowledge of the scattering properties

This study presents a methodology to accurately extract the absorption coefficient from single fiber reflectance spectra measured in turbid media without a priori knowledge of either the reduced scattering coefficient or the phase function. This novel approach accounts for the interrelated effects these properties have on the photon path length, yielding estimates of an absorption coefficient on average within <7.5% of true values over a wide range of biologically relevant optical properties.     

Nonlinear Instability of the Two-Dimensional Striation Model About Smooth Steady States

The two-dimensional striation model consists of a nonlinear system of PDE's which arises in the modeling of the ionospheric plasma. The local-in-time existence of strong solutions is first proved using Banach's fixed point theorem. Then, under physically relevant assumptions, the system is shown to be nonlinearly unstable as soon as it is linearly unstable. Moreover, the instability occurs before the possible blow-up time of the solution. The proof relies on an earlier work of Hwang and Guo (2003 Hwang , H. J. , Guo , Y. ( 2003 ). On the dynamical Rayleigh–Taylor instability . Arch. of Rat. Mech. Anal. 167 : 235 – 253 .[Crossref], [Web of Science ®] , [Google Scholar]). The first step of the proof is to investigate under which conditions the linearized system is unstable and to prove that its spectrum is bounded, by means of a variational formulation. The second one consists in constructing a family of solutions depending on the parameter δ measuring the smallness of the perturbation to the steady-state. Thanks to the boundedness of the linearized spectrum, this family of solutions is shown to be unstable by means of a power series expansion in δ.     

Modeling,Analysis, and Simulation of Biofilm Formation and Decay

In this article, we give a brief overview of our recent work on continuum mechanical modelling and simulation of microbial films. This comprises some classical tasks of applied mathematics such as computational fluid dynamics, analysis of partial differential equations, and mathematical biology.     

Fractionated Illumination at Low Fluence Rate Photodynamic Therapy in Mice

Photodynamic therapy (PDT) for actinic field cancerization is effective but painful. Pain mechanisms remain unclear but fluence rate has been shown to be a critical factor. Lower fluence rates also utilize available oxygen more efficiently. We investigated PDT effect in normal SKH1-HR mice using low and high fluence rate aminolevulinic acid (ALA) PDT and a fractionated illumination scheme. Six groups of six mice with different light treatment parameters were studied. Visual skin damage was assessed up to 7 days post-PDT. Fluorescence and reflectance spectroscopy during illuminations provided us with real-time information about protoporphyrin IX (PpIX) photobleaching. A novel dosing approach was introduced in that we used a photobleaching percentage instead of a preset fluence. Data show similar total and maximum damage scores in high and low fluence rate groups. Photobleaching of PpIX in the low fluence rate groups shows a trend toward more efficient photobleaching. Results indicate that low fluence rate PDT is as effective as and more efficient than high fluence rate PDT in normal mouse skin. Low fluence rate PDT light protocols need to be explored in human studies in search for an effective and well-tolerated treatment for actinic field cancerization.     

Subsampling effects in neuronal avalanche distributions recorded in vivo

Background  

Many systems in nature are characterized by complex behaviour where large cascades of events, or avalanches, unpredictably alternate with periods of little activity. Snow avalanches are an example. Often the size distribution f(s) of a system's avalanches follows a power law, and the branching parameter sigma, the average number of events triggered by a single preceding event, is unity. A power law for f(s), and sigma = 1, are hallmark features of self-organized critical (SOC) systems, and both have been found for neuronal activity in vitro. Therefore, and since SOC systems and neuronal activity both show large variability, long-term stability and memory capabilities, SOC has been proposed to govern neuronal dynamics in vivo. Testing this hypothesis is difficult because neuronal activity is spatially or temporally subsampled, while theories of SOC systems assume full sampling. To close this gap, we investigated how subsampling affects f(s) and sigma by imposing subsampling on three different SOC models. We then compared f(s) and sigma of the subsampled models with those of multielectrode local field potential (LFP) activity recorded in three macaque monkeys performing a short term memory task.     

Über einen zusammenhang zwischen gewissen linearen differential- und differenzengleichungen

Ohne Zusammenfassung     

The dose-response relationship for tumourigenesis by UV radiation in the region 311-312 nm

Groups of hairless mice were irradiated daily with Philips TL01 UVB sources. This type of lamp has become available recently and was developed for UVB phototherapy of psoriasis. The TL01 emits radiation in a narrow band around 311-312 nm. Tumours developed on all animals. The dose-response relationship had practically the same shape as that found in a similar experiment with Westinghouse FS40 sunlamps; the tumour induction time appeared to be proportional to the daily dose to a power of -0.58. An additional experiment was performed with a TL01 from which the shorter wavelengths were filtered away. This reduced the carcinogenic effectiveness by a factor of 2.3. The potential of the filtered lamp for phototherapy of psoriasis is discussed.     

Physicochemical characterization of the endotoxins from Coxiella burnetii strain Priscilla in relation to their bioactivities

Background  

Coxiella burnetiiis the etiological agent of Q fever found worldwide. The microorganism has like other Gram-negative bacteria a lipopolysaccharide (LPS, endotoxin) in its outer membrane, which is important for the pathogenicity of the bacteria. In order to understand the biological activity of LPS, a detailed physico-chemical analysis of LPS is of utmost importace.