Enzyme replacement therapies: What is the best option?

Despite many beneficial outcomes of the conventional enzyme replacement therapy (ERT), several limitations such as the high-cost of the treatment and various inadvertent side effects including the occurrence of an immunological response against the infused enzyme and development of resistance to enzymes persist. These issues may limit the desired therapeutic outcomes of a majority of the lysosomal storage diseases (LSDs). Furthermore, the biodistribution of the recombinant enzymes into the target cells within the central nervous system (CNS), bone, cartilage, cornea, and heart still remain unresolved. All these shortcomings necessitate the development of more effective diagnosis and treatment modalities against LSDs. Taken all, maximizing the therapeutic response with minimal undesired side effects might be attainable by the development of targeted enzyme delivery systems (EDSs) as a promising alternative to the LSDs treatments, including different types of mucopolysaccharidoses (MPSs ) as well as Fabry, Krabbe, Gaucher and Pompe diseases

Effects of process variables on micromeritic properties and drug release of non-degradable microparticles

Introduction: The purpose of this investigation was to evaluate microencapsulated controlled release preparation of theophylline using Eudragit RS 100 as the retardant material with high entrapment efficiency. Methods: Microspheres were prepared by the emulsion-solvent evaporation method. A mixed solvent system consisting of methanol and acetone and light liquid paraffin as oily phase were chosen. Sucrose stearate was used as the surfactant to stabilize the emulsification process. The prepared microspheres were characterized by drug loading, Fourier-transform infrared spectroscopy (FTIR), differential scanning colorimetry (DSC) and scanning electron microscopy (SEM). The in vitro release studies were performed at pH 1.2 and 7.4 aqueous medium. Results: Increasing the concentration of emulsifier, sucrose fatty acid ester F-70, decreased the particle size which contributed to increased drug release rate. The drug loading microparticle Eudragit RS100(1:6) showed 60-75% of entrapment and mean particle size 205.93-352.76 μm.The results showed that, an increase in the ratio of polymer: drug (F5, 6: 1) resulted in a reduction in the release rate of the drug which may be attributed to the hydrophobic nature of the polymer. Conclusion: The release of theophylline is influenced by the drug to polymer ratio and particle size. Drug release is controlled by diffusion and the best-fit release kinetic is Higuchi model. © 2011 by Tabriz University of Medical Sciences

Niche inheritance: a cooperative pathway to enhance cancer cell fitness though ecosystem engineering

Cancer cells can be described as an invasive species that is able to establish itself in a new environment. The concept of niche construction can be utilized to describe the process by which cancer cells terraform their environment, thereby engineering an ecosystem that promotes the genetic fitness of the species. Ecological dispersion theory can then be utilized to describe and model the steps and barriers involved in a successful diaspora as the cancer cells leave the original host organ and migrate to new host organs to successfully establish a new metastatic community. These ecological concepts can be further utilized to define new diagnostic and therapeutic areas for lethal cancers.Comment: 8 pages, 1 Table, 4 Figure

Targeted Fluoromagnetic Nanoparticles for Imaging of Breast Cancer MCF-7 Cells

Purpose: To achieve simultaneous imaging and therapy potentials, targeted fluoromagnetic nanoparticles were synthesized and examined in human breast cancer MCF-7 cells. Methods: Fe3O4 nanoparticles (NPs) were synthesized through thermal decomposition of Fe(acac)3. Then, magnetic nanoparticles (MNPs) modified by dopamine-poly ethylene glycol (PEG)-NH2; finally, half equivalent fluorescein isothiocyanate (FITC) and half equivalent folic acid were conjugated to one equivalent of it. The presence of Fe3O4-DPA-PEG-FA/FITC in the folate receptor (FR) positive MCF-7 cells was determined via fluorescent microscopy to monitor the cellular interaction of MNPs. Results: FT-IR spectra of final compound confirmed existence of fluorescein on folic acid grafted MNPs. The Fe3O4-DPA-PEG-FA/FITC NPs, which displayed a size rang about 30-35 nm using scanning electron microscopy (SEM) and transmission electron microscopy (TEM), were able to actively recognize the FR-positive MCF-7 cells, but not the FR-negative A549 cells. Conclusion: The uniform nano-sized Fe3O4-DPA-PEG-FA/FITC NPs displayed great potential as theranostics and can be used for targeted imaging of various tumors that overexpress FR

Flash Cooking: Phase Change Thermal Storage with Solar Salt

After a few hours of sun, the solar salt Insulated Solar Electric Cooker (ISECooker) can deliver up to 0.7 kWh of energy to the contents of a cookpot. In the first 2 minutes of cooking, the ISECooker provides an average ~5000 W to the food, resulting in “flash cooking.” Molten solar salt holds solar electric energy in an insulated chamber, allowing a user to cook in the evening, hours after the sun has set. A global group of collaborators is working to optimize the construction, dissemination and designs of ISECookers

Times-History Finite Element Dynamic Analysis - Soil Nail Wall - San Manuel Casino - Highland, California

The site of the proposed Phase II Parking Facility at the San Manuel Resort Casino, Highland, California, is on a sloped terrain where there is a 35 ft. grade differential from the north to the south end of the planned structure. PB&A, Inc. was selected to design a 12,000 square foot Soil-Nailed wall with a maximum height of 37 ft. to protect the Parking Structure from the soil pressures resulting from sloping ground conditions at the site. The project site is located within 100 feet of the San Andreas Fault in the highly seismic Southern California region, characterized by numerous active faults and high level seismic activity. The alignment of the Soil-Nailed wall is located at the edge of the Alquist-Priolo Earthquake Fault Zone. The proximity of the Soil Nail Wall to this major seismic fault necessitated the preparation of a dynamic analysis to better assess the behavior of the wall during a seismic event. The main objective of this analysis was to determine the maximum deformation the Soil-Nailed Wall would undergo during an earthquake so that an adequate separation could be defined between the structure of the parking garage and the Soil-Nailed Wall. In addition, vertical soil nails (V-Nails) were to be installed directly behind the shotcrete facing of the wall to provide localized surface stability during construction. The effect of the V-Nails was to be studied in relationship to the overall performance of the wall. The Geotechnical Engineer of Record, Kleinfelder, provided three sets of spectra-matched outcropping acceleration time histories from three representative earthquakes: Duzce earthquake, Turkey (11/12/1999), Landers earthquake, United States (06/28/1992) and Chi-Chi earthquake, Taiwan China (09/20/1999). Using the information gleaned from these time histories, PB&A constructed a half-space model in PLAXIS, a Finite Element software application widely used in the industry. To construct the model, engineers used the Mohr-Columb soil model applied to layers of soil at the project site. The soil strength and stiffness parameters were based on the recommended values outlined in the Geotechnical Report and the shotcrete wall and soil nails were modeled with the plate (Beam) and ground anchor element, respectively. It was necessary to transform the acceleration time histories to the proper depth at the bottom of the PLAXIS model, as the acceleration time histories were recorded as the outcropping motions,. To accomplish this, the deconvolution process was performed in the SHAKE91 program. In the staged construction calculation, the horizontal and vertical displacement, velocity and acceleration are recorded at the top and the bottom of the wall in each step

Transmission Control Protocol over Wireless LAN

802.11 standards based WLAN is one very successful technology in commerce. Huge number of WLAN has been deployed across the world. It2019;s very worthwhile to investigate link characteristics of WLAN and its effects to upper layers, especially TCP protocol which is used by numerous network applications. The 802.11 standard is firstly introduced in this section