The development of an in-vivo method for assessing the antithrombotic properties of pharmaceutical compounds

The formation of a thrombus stems from the malfunction of a normal physiological function referred to as haemostasis and the activity of blood platelets; such thrombi give rise to debilitating and often fatal strokes. Consequently much effort is associated with the search for pharmacological compounds capable of their prevention or dispersion. · Most of the primary screens associated with such work rely on in-vitro tests and in separating the blood from it's vasculature, the influence and results associated with several naturally occuring moderators may be lost. There therefore exists the incentive to develop more representative in-vivo screening methods. Following an introduction to the underlying physiology and pharmacology and a review of established screening methods, this thesis proceeds to describe the development of a novel technique suitable for such in-vivo studies. It's inception is shown to be a consequence of an amalgamation of ultrasonic methods associated with the clinical detection of occlusions and laser Doppler velocimetry. Both topics are individually surveyed and then brought together through a concept whereby the efficacy of compounds might be evaluated in animal models by measuring the velocity of blood in the fluid jet formed distal to an induced thrombus.The main underlying assumption is that the jet velocity will reflect the degree of encroachment of the thrombus into the vasculature. In accord with the evolved measurement rationale there then follows a description of a specific laser Doppler velocimeter and some associated experiments, designed to qualitatively appraise the validity of the underlying assumptions. The ensuing results in turn give rise to the design of a laser Doppler microscope, an analyser for extracting the required velocity information from the Doppler shift spectrum and an additional series of experiments. Central to this latter stage of validation is the use of a thrombus analogue in a narrow bored glass flow tube. Finally, some preliminary in-vivo experiments and results are presented

Aerospace medicine and biology: A continuing bibliography with indexes (supplement 335)

This bibliography lists 143 reports, articles and other documents introduced into the NASA Scientific and Technical Information System during March, 1990. Subject coverage includes: aerospace medicine and psychology, life support systems and controlled environments, safety equipment, exobiology and extraterrestrial life, and flight crew behavior and performance

Impact of the different preparation methods to obtain human adipose-derived stromal vascular fraction cells (AD-SVFs) and human adipose-derived mesenchymal stem cells (AD-MSCs): Enzymatic digestion versus mechanical centrifugation

Autologous therapies using adipose-derived stromal vascular fraction (AD-SVFs) and adult adipose-derived mesenchymal stem cells (AD-MSCs) warrant careful preparation of the harvested adipose tissue. Currently, no standardized technique for this preparation exists. Processing quantitative standards (PQSs) define manufacturing quantitative variables (such as time, volume, and pressure). Processing qualitative standards (PQLSs) define the quality of the materials and methods in manufacturing. The purpose of the review was to use PQSs and PQLSs to report the in vivo and in vitro results obtained by different processing kits that use different procedures (enzymatic vs. non-enzymatic) to isolate human AD-SVFs/AD-MSCs. PQSs included the volume of fat tissue harvested and reagents used, the time/gravity of centrifugation, and the time, temperature, and tilt level/speed of incubation and/or centrifugation. PQLSs included the use of a collagenase, a processing time of 30 min, kit weight, transparency of the kit components, the maintenance of a closed sterile processing environment, and the use of a small centrifuge and incubating rocker. Using a kit with the PQSs and PQLSs described in this study enables the isolation of AD-MSCs that meet the consensus quality criteria. As the discovery of new critical quality attributes (CQAs) of AD-MSCs evolve with respect to purity and potency, adjustments to these benchmark PQSs and PQLs will hopefully isolate AD-MSCs of various CQAs with greater reproducibility, quality, and safety. Confirmatory studies will no doubt need to be completed

Aerospace medicine and biology: A continuing bibliography with indexes, supplement 218, April 1981

This bibliography lists 161 reports, articles, and other documents introduced into the NASA scientific and technical information system in March 1981

Aerospace Medicine and Biology: A continuing bibliography with indexes (supplement 153)

This bibliography lists 175 reports, articles, and other documents introduced into the NASA scientific and technical information system in March 1976

The State of the Art in Endodontics

Nowadays, we use the term “modern endodontics” thanks to new technologies, novel materials, and revolutionary techniques. Various equipment is available to facilitate and improve our endodontic treatments, such as operating microscopes, ultrasounds, lasers, modern alloys for rotary files, powerful irrigation systems, new materials for filling root canals, 3D radiology, and several more. With the aid of the previously mentioned advances, complex endodontic treatments can be carried out safely, hence guaranteeing patients a high level of care and, above all, saving teeth that would otherwise be doomed for extraction. General practitioners and, even more importantly, specialists in endodontics should implement these modern technologies in their practice. This Special Issue will focus on modern endodontics regarding all the recent updates. Full papers of original articles, short communications, and review articles are all invited

Polymer-clay Nanocomposites

PhDPolymer-clay nanocomposites are attracting global interest principally because property enhancements are obtained at low clay particle loadings (1-5 wt%). However there is lack of fundamental understanding of such composites. The aim of this work is to provide an insight into the interaction between polymer and clay. This includes the driving force for intercalation, the reinforcement mechanisms and property-volume fraction relationships. Functionalised poly(ethylene glycol)-clay, poly(c-caprolactone)-clay and thermoplastic starch-clay nanocomposites with a range of polymer molecular weights, clay volume fractions and with different clays were prepared using solution methods, melt-processing methods, and in situ polymerisation. A reliable X-ray diffraction technique for low angle basal plane spacing of clay, the essential parameter for structure determination, was established obtaining ±0.005 Mn between three diffractometers. The basal plane spacing was found to be unaffected by polymer molecular weight and preparation method but was affected by the nature of the polymer and clay. Increasing clay loading could lead to a lower spacing. As a cautionary observation, poly(ethylene glycol) with high molecular weight (2: 10,000) was found to undergo degradation readily during preparation of nanocomposites with and without clay. Competitive sorption experiments for molecular weight showed that high molecular weight fractions of polymer intercalate preferentially into clay during solution preparation. Thermodynamic studies on the intercalation process found that significant enthalpic change occurred during intercalation, which is coincident with the observation that heat-treated clays without interlayer water can intercalate polymer. The calculation of true volume fraction against nominal volume fraction provided reasonable explanation of property enhancement and helps understand the relation between nanocomposites and conventional composites. At a given clay loading, nanocomposites with better dispersion gave more property enhancement than those with lower dispersion or conventional composites. The crystallinity of semicrystalline polymer was also affected by varying extents of dispersion of clay. The use of X-ray diffraction with an internal standard was explored for quantitative analysis of intercalation and exfoliation

The role of ultrasound-driven microbubble dynamics in drug delivery : from microbubble fundamentals to clinical translation

In the last couple of decades, ultrasound-driven microbubbles have proven excellent candidates for local drug delivery applications. Besides being useful drug carriers, microbubbles have demonstrated the ability to enhance cell and tissue permeability and, as a consequence, drug uptake herein. Notwithstanding the large amount of evidence for their therapeutic efficacy, open issues remain. Because of the vast number of ultrasound- and microbubble-related parameters that can be altered and the variability in different models, the translation from basic research to (pre)clinical studies has been hindered. This review aims at connecting the knowledge gained from fundamental microbubble studies to the therapeutic efficacy seen in in vitro and in vivo studies, with an emphasis on a better understanding of the response of a microbubble upon exposure to ultrasound and its interaction with cells and tissues. More specifically, we address the acoustic settings and microbubble-related parameters (i.e., bubble size and physicochemistry of the bubble shell) that play a key role in microbubble cell interactions and in the associated therapeutic outcome. Additionally, new techniques that may provide additional control over the treatment, such as monodisperse microbubble formulations, tunable ultrasound scanners, and cavitation detection techniques, are discussed. An in-depth understanding of the aspects presented in this work could eventually lead the way to more efficient and tailored microbubble-assisted ultrasound therapy in the future