Protein-repellent and antimicrobial nanoparticle coatings from hyaluronic acid and a lysine-derived biocompatible surfactant.

Biofilm formation triggered by uncontrolled protein adsorption, on medical devices is the leading cause of catheter-associated urinary tract infections (CAUTI) during implantation. Herein, we report a water-based, green and one-step strategy to functionalize surfaces of silicone catheters, poly(dimethylsiloxane) (PDMS), with antifouling and antimicrobial substances to avoid uncontrolled protein adsorption and microbial attachment. A novel synergetic formulation consisting of an anionic glycosaminoglycan (hyaluronic acid, HA) and a lysine-derived biocompatible cationic surfactant (Nε-myristoyl-lysine methyl ester, MKM) was prepared, resulting in the formation of nanoparticles (NPs, ca. 100-250 nm). Besides their high stability and long-lasting hydrophilicity in ambient and aqueous environments for 60 days, the nanometric layers (48 ± 3 nm) of HA-MKM NPs on PDMS showed no adsorption of BSA and lysozyme and substantially lower adsorption of fibrinogen as revealed by a quartz crystal microbalance with dissipation (QCM-D). In vitro antimicrobial test with S. aureus, E. coli, P. aeruginosa, P. mirabilis, C. albicans microbes under dynamic conditions revealed that the microbial growth was hampered by 85% compared with unmodified PDMS. Given the multiple functionalities, charges and diverse physiochemical properties of polysaccharide-lysine-based surfactant mixtures, this approach can be easily extended to the development of novel coatings on other silicone-based materials, thereby broadening potential applicability of PDMS-based biomaterials/devices in microfluidics, diagnostic biosensors and others.

Wavelet analysis of oscillations in the peripheral blood circulation measured by laser Doppler technique.

The wavelet transform technique, a time-frequency method with logarithmic frequency resolution, was used to analyze oscillations in human peripheral blood flow measured by laser Doppler flowmetry. The oscillations extended over a wide frequency scale and their periods varied in time. Within the frequency range studied, 0.0095-1.6 Hz, five characteristic oscillations were revealed, arising from both local and central regulatory mechanisms. After the insertion of endothelium-dependent and endothelium-independent vasodilators the spectra of blood flow markedly differed in the frequency interval 0.0095-0.02 Hz. In this way it was demonstrated that endothelial activity is a rhythmic process that contributes to oscillations in blood flow with a characteristic frequency of around 0.01 Hz. The study illustrates the potential of laser Doppler flowmetry combined with dynamical systems analysis for studies of both the micro- and macroscopic mechanisms of blood flow regulation in vivo.

Linear and nonlinear analysis of blood flow in healthy subjects and in subjects with Raynaud's phenomenon.

The paper presents analyses of the dynamics contained in the blood flow signals measured on healthy subjects and on subjects with primary Raynaud's phenomenon. Different signal processing methods are presented and discussed. The dynamics was evaluated in the time and frequency domains and in phase space. Additionally, changes in the basal value during temperature provocation were studied using multiresolution analysis. The analyses demonstrate differences between the blood flow dynamics in healthy subjects and subjects with Raynaud's phenomenon. Moreover, the observed decrease in the amplitude of oscillation in regions approximately 0.04 Hz and approximately 0.1 Hz suggests an impairment in the neurogenic and the myogenic regulation of the blood flow. The administration of nifedipine in subjects with Raynaud's phenomenon results in an increase in the basal value and in the amplitude of the blood flow component oscillating with the heart rate. However, it does not restore the dynamics to that found in healthy subjects.

Spectral analysis of the laser Doppler perfusion signal in human skin before and after exercise.

Spectral analysis based on wavelet transformation of the periodic oscillations of the cutaneous laser Doppler flowmetry (LDF) signal was used to analyze exercise-induced changes in flow motion in humans. The measurements were performed on the forearm skin in nine healthy, less-trained subjects before and after exercise. Periodic oscillations with frequencies of around 1, 0.3, 0.1, and 0.04 Hz were demonstrated, which are proposed to represent the influence of heart beat, respiration, intrinsic myogenic activity, and the neurogenic factors, respectively, on cutaneous blood flow. We also demonstrated oscillations with a frequency of around 0.01 Hz both before and after exercise. The mean spectral amplitude in the frequency range from 0.0095 to 2.3 Hz increased twofold (P = 0.004) in response to exercise. This increase results from a significant increase in the amplitude of oscillations of around 1, 0.3, and 0.1 Hz. The amplitude of oscillations of around 1 and 0.3 Hz increased onefold in response to exercise (P = 0.02 for both frequencies), whereas the amplitude of oscillations of around 0.1 Hz increased threefold (P = 0.008). Furthermore, to evaluate relative changes of each particular oscillation in response to exercise, the absolute amplitude of each frequency interval was divided by the mean spectral amplitude. In this way, the relative contribution of oscillations of around 0.01 and 0.04 Hz were shown to decrease significantly following exercise (P = 0.008 and P = 0.004, respectively). The relative contribution of the oscillations of around 0.1 Hz increased, although not statistically significant (P = 0.08), while the relative contribution of the oscillations of around 0.3 and 1 Hz to the total flow motion remained unchanged in response to exercise (P = 0.84 and P = 0.95, respectively). These findings indicate an increased contribution of the oscillations of around 0.1 Hz to the regulation of the cutaneous blood flow following exercise, whereas oscillations of around 0.04 and 0.01 Hz contribute less. We conclude that spectral analysis using a wavelet transformation of the LDF signal is a valuable tool for use in the evaluation of exercise-induced changes in the dynamics of cutaneous microvascular blood flow, but further studies are necessary to clarify the physiological origin of these oscillations.

Wavelet-based analysis of human blood-flow dynamics.

To analyze signals measured from human blood flow in the time-frequency domain, we used the wavelet transform which gives good time resolution for high-frequency components and good frequency resolution for low-frequency components. Five characteristic frequency peaks, corresponding to five almost periodic rhythmic activities, were found on the time scale of minutes. These oscillations were characterized by time and spatial invariant measures. The potential of this approach in studying the blood-flow dynamics was illustrated by revealing differences between the groups of control subjects and athletes.

Nonlinear dynamics of the blood flow studied by Lyapunov exponents.

In order to gain an insight into the dynamics of the cardiovascular system throughout which the blood circulates, the signals measured from peripheral blood flow in humans were analyzed by calculating the Lyapunov exponents. Over a wide range of algorithm parameters, paired values of both the global and the local Lyapunov exponents were obtained, and at least one exponent equaled zero within the calculation error. This may be an indication of the deterministic nature and finite number of degrees of freedom of the cardiovascular system governing the blood-flow dynamics on a time scale of minutes. A difference was observed in the Lyapunov dimension of controls and athletes.