Encapsulation of Antimicrobial Peptides in Bicontinuous Microemulsions for Topical Delivery to Surgical Site Infections and Chronic Wounds

Surgical site infections and chronic wounds, especially those caused by antibiotic-resistant microorganisms, result in hospitalization and fatalities each year. Methods to prevent these infections, such as cleaning and preparing medical tools, have had minimal success in preventing infections. Further, antibiotic treatments have become less successful in treating infections and wounds because of antibiotic-resistant bacteria. Antimicrobial peptides (AMP) are a possible treatment solution for wound infections. AMPs are oligopeptides that occur in nature or can be synthesized in vitro which possess a broad spectrum of antimicrobial activity against bacteria and other harmful microorganisms. AMPs operate by disrupting the packing arrangements of biomembranes in prokaryotes through their insertion into negatively charged phospholipid bilayers. However, many AMP products fail clinical trials because of their difficulty to be encapsulated and delivered at high concentrations in an active form. This project proposed the use of bicontinuous microemulsions (BMEs) as a possible system to encapsulate and deliver AMPs. BMEs are thermodynamically stable mixtures consisting of a surfactant, oil, aqueous mixture, and sometimes a cosurfactant. They are optically clear and the surfactant(s) in BMEs solubilize nearly equal amounts of oil and water creating elongated nanodomains. AMPs are typically cationic, and the following hypothesis was tested: BMEs created with anionic surfactants would induce a more highly folded, hence more biologically active, conformation for melittin. Several different BME systems composed of biocompatible oils were identified and evaluated for their ability to encapsulate melittin, a model AMP, and to test the system’s antimicrobial activity. Small-angle x-ray scattering showed melittin effected the BMEs quasi-periodic repeat distance and correlation lengths. Circular dichroism data showed a higher percentage of melittin was in its active form when encapsulated in a BME compared to an aqueous solution. Fluorescence measurements showed melittin resided within the surfactant monolayers of the BMEs. Antimicrobial diffusion assays proved that there was a larger zone of inhibition against bacteria commonly found in surgical site infections and chronic wounds than the BMEs without melittin. This research was successful in adding an AMP into BMEs created with biocompatible materials and may be a viable option in combating the rise in antibiotic-resistant organisms

Certain Elastic Properties of Phosphor-Bronze Wires

The work by Guthe, Guthe and Sieg, and Sieg, on platinumiridium wires when used as suspensions for torsion pendulums, showed some remarkable elastic properties of that alloy. The principal one of these was the variation of the period with the amplitude of vibration. It was these studies that made it seem very desirable to test other alloys commonly used for suspensions, by a similar method

Handling and analysis of ices in cryostats and glove boxes in view of cometary samples

Comet nucleus sample return mission and other return missions from planets and satellites need equipment for handling and analysis of icy samples at low temperatures under vacuum or protective gas. Two methods are reported which were developed for analysis of small icy samples and which are modified for larger samples in cometary matter simulation experiments (KOSI). A conventional optical cryostat system was modified to allow for transport of samples at 5 K, ion beam irradiation, and measurement in an off-line optical spectrophotometer. The new system consists of a removable window plug containing nozzles for condensation of water and volatiles onto a cold finger. This plug can be removed in a vacuum system, changed against another plug (e.g., with other windows (IR, VIS, VUV) or other nozzles). While open, the samples can be treated under vacuum with cooling by manipulators (cut, removal, sample taking, irradiation with light, photons, or ions). After bringing the plug back, the samples can be moved to another site of analysis. For handling the 30 cm diameter mineral-ice samples from the KOSI experiments an 80x80x80 cm glove box made out of plexiglass was used. The samples were kept in a liquid nitrogen bath, which was filled from the outside. A stream a dry N2 and evaporating gas from the bath purified the glove box from impurity gases and, in particular, H2O, which otherwise would condense onto the samples

Notes on Certain Elastic Peculiarities of Phosphor Bronze Wires

Some previous work by one of the authors with wires of an alloy of platinum-iridium, portions of which work were published in these Proceedings, indicated that when the wires were used as suspensions for torsion pendulums, the relations between the period of vibration and the amplitude were exceedingly complicated. The effect of drawing these wires was dealt with in another paper. In all these papers referred to, the statement was made that similar tests should be applied to some of the more common wires in the hope of finding similar, even though smaller effects. Through press of work these experiments have been deferred until the present year. This particular paper will deal with but one feature of the work, namely, the effect of drawing on the elastic nature of phosphor bronze wires. The writers are indebted to the American Electrical Works, of Phillipsdale, Rhode Island, for kindly furnishing them with specimens of the wires

Hitzschlag mit Alpha-Koma: Ein Fallbericht

Zusammenfassung: Wir berichten über einen 41-jährigen komatösen Patienten, der einen schwer verlaufenden Hitzschlag mit einer Körperkerntemperatur von 41,5°C erlitt. Der klinische Verlauf wurde kompliziert durch eine akute systemische inflammatorische Reaktion und Multiorganversagen. Das EEG zeigte ein prognostisch ungünstiges Alpha-Koma ohne Reaktivität auf externe Stimuli. Der Patient erlangte das Bewusstsein wieder und wurde nach 16Tagen aus der intensivmedizinischen Behandlung entlassen. Im weiteren Verlauf entwickelte sich eine zerebrale Toxoplasmose, die mit einer Kombinationstherapie aus Sulfadiazin und Pyrimethamin behandelt wurde. Nach 65Tagen erfolgte eine Verlegung in eine Neurorehabilitationsklinik mit einem moderaten neurologischen Defizi

High-energy picosecond Nd:YVO4 slab amplifier for OPCPA pumping

We demonstrate 12-ps pulses with up to 0.6-mJ pulse energy at repetition rates of 50 kHz and 100 kHz from a Nd:YVO4 slab amplifier built in a simple four-pass configuration. Excellent noise performance with pulse energy fluctuations below 0.8% rms has been achieved by using 10-μJ seed pulses from a highly stable industrial laser system and moderate gain (30-46) in the slab amplifie

Description of non-specific DNA-protein interaction and facilitated diffusion with a dynamical model

We propose a dynamical model for non-specific DNA-protein interaction, which is based on the 'bead-spring' model previously developed by other groups, and investigate its properties using Brownian Dynamics simulations. We show that the model successfully reproduces some of the observed properties of real systems and predictions of kinetic models. For example, sampling of the DNA sequence by the protein proceeds via a succession of 3d motion in the solvent, 1d sliding along the sequence, short hops between neighboring sites, and intersegmental transfers. Moreover, facilitated diffusion takes place in a certain range of values of the protein effective charge, that is, the combination of 1d sliding and 3d motion leads to faster DNA sampling than pure 3d motion. At last, the number of base pairs visited during a sliding event is comparable to the values deduced from single-molecule experiments. We also point out and discuss some discrepancies between the predictions of this model and some recent experimental results as well as some hypotheses and predictions of kinetic models

Antibody-based immunotherapy for ovarian cancer: where are we at?

Cytoreductive surgery and chemotherapy continue to be the mainstay of ovarian cancer treatment. However, as mortality from advanced ovarian cancer remains very high, novel therapies are required to be integrated into existing treatment regimens. Immunotherapy represents an alternative and rational therapeutic approach for ovarian cancer based on a body of evidence supporting a protective role of the immune system against these cancers, and on the clinical success of immunotherapy in other malignancies. Whether or not immunotherapy will have a role in the future management of ovarian cancer is too early to tell, but research in this field is active. This review will discuss recent clinical developments of selected immunotherapies for ovarian cancer which fulfil the following criteria: (i) they are antibody-based, (ii) target a distinct immunological pathway, and (iii) have reached the clinical trial stage. Specifically, the focus is on Catumaxomab (anti-EpCAM × anti-CD3), Abagovomab, Oregovomab (anti-CA125), Daclizumab (anti-CD25), Ipilimumab (anti-CTLA-4), and MXD-1105 (anti-PD-L1). Catumaxomab has reached phase III clinical trials and exhibits promise with reports, showing that it can cause a significant and sustained reduction in ascites. Phase I-III clinical trials continue to be conducted on the other antibodies, some of which have had encouraging reports. We will also provide our perspective on the future of immunotherapy for ovarian cancer, and how it may be best employed in treatment regimen

Self-referencable frequency comb from a 170-fs, 1.5-μm solid-state laser oscillator

We report measurement of the first carrier-envelope offset (CEO) frequency signal from a spectrally broadened ultrafast solid-state laser oscillator operating in the 1.5μm spectral region. The f-to-2f CEO frequency beat signal is 49 dB above the noise floor (100-kHz resolution bandwidth) and the free-running linewidth of 3.6 kHz is significantly better than typically obtained by ultrafast fiber laser systems. We used a SESAM mode-locked Er:Yb:glass laser generating 170-fs pulses at a 75MHz pulse repetition rate with 110-mW average power. It is pumped by one standard telecom-grade 980-nm diode consuming less than 1.5W of electrical power. Without any further pulse compression and amplification, a coherent octave-spanning frequency comb is generated in a polarization-maintaining highly-nonlinear fiber (PM-HNLF). The fiber length was optimized to yield a strong CEO frequency beat signal between the outer Raman soliton and the spectral peak of the dispersive wave within the supercontinuum. The polarization-maintaining property of the supercontinuum fiber was crucial; comparable octave-spanning supercontinua from two non-PM fibers showed higher intensity noise and poor coherence. Astable CEO-beat was observed even with pulse durations above 200fs. Achieving a strong CEO frequency signal from relatively long pulses with moderate power levels substantially relaxes the demands on the driving laser, which is particularly important for novel gigahertz diode-pumped solid-state and semiconductor laser