Improved cellular infiltration into nanofibrous electrospun crosslinked gelatin scaffolds templated with micrometer sized polyethylene glycol fibers

Gelatin-based nanofibrous scaffolds with a mean fiber diameter of 300 nm were prepared with and without micrometer-sized polyethylene glycol (PEG) fibers that served as sacrificial templates. Upon fabrication of the scaffolds via electrospinning, the gelatin fibers were crosslinked with glutaraldehyde, and the PEG templates were removed using tert-butanol to yield nanofibrous scaffolds with pore diameters ranging from 10 to 100 μm, as estimated with mercury intrusion porosimetry. Non-templated gelatin-based nanofibrous matrices had an average pore size of 1 μm. Fibroblasts were seeded onto both types of the gelatin-based nanfibrous surfaces and cultured for 14 days. For comparative purposes, chitosan-based and polyurethane (PU)-based macroporous scaffolds with pore sizes of 100 μm and 170 μm, respectively, also were included. The number of cells as a function of the depth into the scaffold was judged and quantitatively assessed using nuclei staining. Cell penetration up to a depth of 250 μm and 90 μm was noted in gelatin scaffolds prepared with sacrificial templates and gelatin-only nanofibrous scaffolds. Noticeably, scaffold preparation protocol presented here allowed the structural integrity to be maintained even with high template content (95 %) and can be easily extended towards other classes of electrospun polymer matrices for tissue engineering

The Effect of Geometrical Factors on the Surface Pressure Distribution on a Human Phantom Model Following Shock Exposure: A Computational and Experimental Study

Experimental data and finite element simulations of an anthropometric surrogate headform was used to evaluate the effect of specimen location and orientation on surface pressures following shock exposures of varying intensity. It was found that surface pressure distributions changed with local flow field disturbances, making it necessary to use data reduction strategies to facilitate comparisons between test locations, shock wave intensities and headform orientations. Non-dimensional parameters, termed amplification factors, were developed to permit direct comparisons of pressure waveform characteristics between incident shock waves differing in intensity, irrespective of headform location and orientation. This approach proved to be a sensitive metric, highlighting the flow field disturbances which exist in different locations and indicating how geometric factors strongly influence the flow field and surface pressure distribution

Glucosamine/L-lactide copolymers as potential carriers for the development of a sustained rifampicin release system using Mycobacterium smegmatis as a tuberculosis model

The present study aims at developing a new, ultrafine particle-based efficient antibiotic delivery system for the treatment of tuberculosis. The carrier material to make the rifampicin (RIF)-loaded particles is a low molecular weight starshaped polymer produced from glucosamine (core building unit) and L-lactide (GluN-LLA). Particles were made via electrohydrodynamic atomization. Prolonged release (for up to 14 days) of RIF from these particles is reported. Drug release data fits the Korsmeyer-Peppas equation, which suggests the occurrence of a modified diffusion-controlled RIF release mechanism in vitro and is also supported by differential scanning calorimetry and drug leaching tests. Cytotoxicity tests on Mycobacterium smegmatis showed that antibiotic-free GluN-LLA and polylactides (PLA) particles (reference materials) did not show any significant anti-bacterial activity. The minimum inhibitory concentration and minimum bactericidal concentration values obtained for RIF-loaded particles showed 2- to 4-fold improvements in the anti-bacterial activity relative to the free drug. Cytotoxicity tests on macrophages indicated that cell death correlates with an increase of particle concentration but is not significantly affected by material type or particle size. Confocal microscopy was used to track internalization and localization of particles in the macrophages. The uptake of GluN-LLA particles is higher than those of their PLA counterparts. In addition, after phagocytosis, the GluN-LLA particles stayed in the cytoplasm and showed favorable long-term drug release behavior, which facilitated the killing of intracellular bacteria when compared to free RIF. The present studies suggest that these drug carrier materials are potentially very attractive candidates for the development of high-payload, sustained-release antibiotic/resorbable polymer particle systems for treating bacterial lung infections

第753回 千葉医学会例会・第一外科教室談話会 26.

<p>The representative incident shock wave profiles generated using helium as a driver gas and Mylar membrane (thickness of 1.016 mm), with accompanying secondary reflected shock and underpressure waves are presented (A). The profile of the secondary wave depends on the gap between the end plate reflector and the exit of the shock tube (B): 1. 0.625-inch, 2. 2-inch, 3. 4-inch, and 4. open end. C. Schematics of the 9-inch square cross section shock tube indicating the breech (I), transition (II), test section (III) and end plate (IV). Distribution of pressure sensor locations is also illustrated. Typically sensors B1, C1, T4, C2, D2 and D4 were used in our experiments to track the shock wave profile evolution along the entire length of the shock tube. The scale bar indicates the distance of specific sensor from the breech, i.e. Mylar membranes installation port.</p

Antioxidant gene therapy against neuronal cell death

Oxidative stress is a common hallmark of neuronal cell death associated with neurodegenerative disorders such as Alzheimer\u27s disease, Parkinson\u27s disease, as well as brain stroke/ischemia and traumatic brain injury. Increased accumulation of reactive species of both oxygen (ROS) and nitrogen (RNS) has been implicated inmitochondrial dysfunction, energy impairment, alterations in metal homeostasis and accumulation of aggregated proteins observed in neurodegenerative disorders, which lead to the activation/modulation of cell death mechanisms that include apoptotic, necrotic and autophagic pathways. Thus, the design of novel antioxidant strategies to selectively target oxidative stress and redox imbalance might represent important therapeutic approaches against neurological disorders. This work reviews the evidence demonstrating the ability of genetically encoded antioxidant systems to selectively counteract neuronal cell loss in neurodegenerative diseases and ischemic brain damage. Because gene therapy approaches to treat inherited and acquired disorders offer many unique advantages over conventional therapeutic approaches, we discussed basic research/clinical evidence and the potential of virus-mediated gene delivery techniques for antioxidant gene therapy

Solution chemistry control to make well defined submicron continuous fibres by electrospinning: the (CH3CH2CH2O)4Ti/AcOH/poly(N-vinylpyrrolidone) system

The (CH3CH2CH2O)4Ti/AcOH/poly(N-vinylpyrrolidone) system has been shown to yield suitable formulations for electrohydrodynamic (EHD) processing into continuous fibres and particles. The EHD processability of this, and generally most sol–gel-based formulations, into well defined fibres and particles with narrow submicron-range diameter distributions depends not only on the EHD process variables (electric field and flow rates), but also on the stability of key physical properties (e.g., conductivity, viscosity, surface tension, density and dielectric constant) of the sol over time. Sols that were almost certainly still undergoing hydrolysis and condensation reactions have been processed via EHD by many research groups to make materials with submicron features. This paper thus highlights the need for understanding the chemistry of EHD-processed solutions to afford reproducibility and near monodispersity in fibre diameter. Reactions were monitored over time with the aid of a flow-through infrared cell, and the structure of species in solution is discussed. Conductivity and viscosity changes with time of representative formulations are discussed in the light of typical EHD processing time scales. Representative sols were processed via EHD, and woven and non-woven fibrous mats were characterized by scanning electron microscopy (SEM)

On the Accurate Determination of Shock Wave Time-Pressure Profile in the Experimental Models of Blast-Induced Neurotrauma

Measurement issues leading to the acquisition of artifact-free shock wave pressure-time profiles are discussed. We address the importance of in-house sensor calibration and data acquisition sampling rate. Sensor calibration takes into account possible differences between calibration methodology in a manufacturing facility, and those used in the specific laboratory. We found in-house calibration factors of brand new sensors differ by less than 10% from their manufacturer supplied data. Larger differences were noticeable for sensors that have been used for hundreds of experiments and were as high as 30% for sensors close to the end of their useful lifetime. These observations were despite the fact that typical overpressures in our experiments do not exceed 50 psi for sensors that are rated at 1,000 psi maximum pressure. We demonstrate that sampling rate of 1,000 kHz is necessary to capture the correct rise time values, but there were no statistically significant differences between peak overpressure and impulse values for low-intensity shock waves (Mach number &lt;2) at lower rates. We discuss two sources of experimental errors originating from mechanical vibration and electromagnetic interference on the quality of a waveform recorded using state-of-the-art high-frequency pressure sensors. The implementation of preventive measures, pressure acquisition artifacts, and data interpretation with examples, are provided in this paper that will help the community at large to avoid these mistakes. In order to facilitate inter-laboratory data comparison, common reporting standards should be developed by the blast TBI research community. We noticed the majority of published literature on the subject limits reporting to peak overpressure; with much less attention directed toward other important parameters, i.e., duration, impulse, and dynamic pressure. These parameters should be included as a mandatory requirement in publications so the results can be properly compared with others

Glucosamine/L-lactide copolymers as potential carriers for the development of a sustained rifampicin release system using Mycobacterium smegmatis as a tuberculosis model

The present study aims at developing a new, ultrafine particle-based efficient antibiotic delivery system for the treatment of tuberculosis. The carrier material to make the rifampicin (RIF)-loaded particles is a low molecular weight starshaped polymer produced from glucosamine (core building unit) and L-lactide (GluN-LLA). Particles were made via electrohydrodynamic atomization. Prolonged release (for up to 14 days) of RIF from these particles is reported. Drug release data fits the Korsmeyer-Peppas equation, which suggests the occurrence of a modified diffusion-controlled RIF release mechanism in vitro and is also supported by differential scanning calorimetry and drug leaching tests. Cytotoxicity tests on Mycobacterium smegmatis showed that antibiotic-free GluN-LLA and polylactides (PLA) particles (reference materials) did not show any significant anti-bacterial activity. The minimum inhibitory concentration and minimum bactericidal concentration values obtained for RIF-loaded particles showed 2- to 4-fold improvements in the anti-bacterial activity relative to the free drug. Cytotoxicity tests on macrophages indicated that cell death correlates with an increase of particle concentration but is not significantly affected by material type or particle size. Confocal microscopy was used to track internalization and localization of particles in the macrophages. The uptake of GluN-LLA particles is higher than those of their PLA counterparts. In addition, after phagocytosis, the GluN-LLA particles stayed in the cytoplasm and showed favorable long-term drug release behavior, which facilitated the killing of intracellular bacteria when compared to free RIF. The present studies suggest that these drug carrier materials are potentially very attractive candidates for the development of high-payload, sustained-release antibiotic/resorbable polymer particle systems for treating bacterial lung infections

Assessment of the Health Risk Related to Air Pollution in Selected Polish Health Resorts

The article discusses the tools used for air quality management in the health resorts in Poland including legal instruments, documents and activities at the regional and local level with an example of formal and legal activities, such as the so-called anti-smog resolution to limit the emission of air pollutants from the municipal and housing sectors and thus minimize the risk related to air pollution. The issue of pollution emission resulting from the spatial conditions, including spatial planning, was also indicated. The analysis of the results pertaining to the PM10 measurements from 2017–2018 available for the resorts in Lower Silesia with reference to selected resorts in other regions of Poland and the health risk assessment according to the concentration-response functions for the PM-based on longand short-term relative risk estimates derived from epidemiological studies were conducted. The exposure assessment was based on the available mathematical modelling results for the PM10 and PM2.5 concentration distributions, which was performed using the CALPUFF model for 2017. In the case of average risk indicators, the obtained values indicated that the values (for all the stays and areas of all zones (total A, B and C) peaked for the Cieplice Śląskie-Zdrój health resort (over 1.1% per annum) and were lowest for Czerniawa and Świeradów-Zdrój (about 0.7%). The highest relative risk indicators in 2017 were observed for cardiovascular diseases for the first two stays in January / February (for the Cieplice Śląskie-Zdrój health resort – over 5%) and for both December stays (over 2.5%). In other health resorts, the risk indicators were significantly lower. The lowest health risk indicators were observed in July, regardless of the location of the health resort and the analysed health effect (rarely exceeding 0.3%). The scale of risk in this case was much higher compared to the short-term risk

Glucosamine/L-lactide copolymers as potential carriers for the development of a sustained rifampicin release system using Mycobacterium smegmatis as a tuberculosis model

The present study aims at developing a new, ultrafine particle-based efficient antibiotic delivery system for the treatment of tuberculosis. The carrier material to make the rifampicin (RIF)-loaded particles is a low molecular weight star-shaped polymer produced from glucosamine (core building unit) and L-lactide (GluN-LLA). Particles were made via electrohydrodynamic atomization. Prolonged release (for up to 14 days) of RIF from these particles is reported. Drug release data fits the Korsmeyer-Peppas equation, which suggests the occurrence of a modified diffusion-controlled RIF release mechanism in vitro and is also supported by differential scanning calorimetry and drug leaching tests. Cytotoxicity tests on Mycobacterium smegmatis showed that antibiotic-free GluN-LLA and polylactides (PLA) particles (reference materials) did not show any significant anti-bacterial activity. The minimum inhibitory concentration and minimum bactericidal concentration values obtained for RIF-loaded particles showed 2- to 4-fold improvements in the anti-bacterial activity relative to the free drug. Cytotoxicity tests on macrophages indicated that cell death correlates with an increase of particle concentration but is not significantly affected by material type or particle size. Confocal microscopy was used to track internalization and localization of particles in the macrophages. The uptake of GluN-LLA particles is higher than those of their PLA counterparts. In addition, after phagocytosis, the GluN-LLA particles stayed in the cytoplasm and showed favorable long-term drug release behavior, which facilitated the killing of intracellular bacteria when compared to free RIF. The present studies suggest that these drug carrier materials are potentially very attractive candidates for the development of high-payload, sustained-release antibiotic/resorbable polymer particle systems for treating bacterial lung infections