Involvement of tissue transglutaminase in the stabilisation of biomaterial/tissue interfaces important in medical devices

Tissue transglutaminase (tTG) has recently been established as a novel cell surface adhesion protein that binds with high affinity to fibronectin in the pericellular matrix. In this study, we have made use of this property to enhance the biocompatibility of poly(epsilon-caprolactone) (PCL), a biomaterial currently used in bone repair. Poly(epsilon-caprolactone) discs were first coated with fibronectin and then tTG. The surface localisation of the two proteins was confirmed using ELISA and the tTG shown to be active on the surface by incorporation of biotin cadaverine into the fibronectin coating. When human osteoblasts (HOBs) were seeded onto the coated polymer surfaces in serum free medium, the surface coated with fibronectin and then tTG showed an increase in the spreading of the cells as compared to the surface coated with fibronectin alone, when analysed using environmental scanning electron microscopy. The presence of tTG had no effect on HOB cell differentiation when analysed by determining alkaline phosphatase activity. The use of tTG as a novel adhesion protein in this way may therefore have considerable potential in forming a stable tissue/biomaterial interface for application in medical devices.

Learning from mother nature:exploiting a biological antioxidant for the melt stabilisation of polymers

An overview of the antioxidant role of the biologically active form of vitamin E, α-tocopherol, in polyolefins is discussed. The effect of the vitamin antioxidant on the melt and colour stability of polyethylene (PE) and polypropylene (PP) is highlighted. It is shown that tocopherol is a highly effective antioxidant that results in superior melt stabilisation of polyolefins particularly when used at much lower concentration than that needed for conventional synthetic hindered phenol processing stabilisers. As with other hindered phenols,α-tocopherol imparts also some colour to the polymer but this is shown to be reduced drastically in the presence of other antioxidants, such as phosphites, or other additives, such as polyhydric alcohols.

Stabilisation and characterisation of peroxide-crosslinked high density polyethylene

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CO-stabilisation mechanisms of nanoparticles and surfactants in Pickering emulsions produced by membrane emulsification

Two different membrane emulsification methods were used to study mechanisms for co-stabilisation of emulsions, by either electrostatic or steric stabilised nanoparticles with anionic, cationic or non-ionic surfactants. The experimental results demonstrated the existence of two distinct co-stabilisation mechanisms that arise from interactions of the nanoparticles and surfactant molecules. When significant interaction is not involved, independent competitive adsorption of nanoparticles and surfactant molecules occurs spontaneously to stabilise droplets in formation. The adsorption/desorption equilibrium between surfactant molecules determines the longevity of the droplet stability. When the surfactant molecule reacts with the nanoparticle surface, the resultant surface modification appears to generate faster wetting kinetics for nanoparticles at the oil/water interface and yields enhanced stabilisation. The paper discusses the implications of controlling these interactions for emulsion production membrane systems.

Thermal stability of porous sol-gel phosphosilicates and their surface area stabilisation by lanthanum addition

The thermal stability of porous sol-gel phosphosilicates was studied by comparing the textural features upon calcination between 400 and 550 °C. A significant loss of surface area and pore volume were observed; the first is due to thermal coarsening of the nanoparticles, and the pore volume reduction was ascribed to sintering of the most external nanoparticles producing less void volume. Lanthanum addition was investigated as thermal stabilizer. For the mesoporous phosphosilicate composition, lanthanum addition enhanced the surface area, showing a 45% and 50% improvement with respect to the La-free counterpart; the effect was much less visible for the macroporous composition.

Stabilisation of dehydrated nanoemulsions using sugar - protein matrices

There are numerous review papers discussing liquid nanoemulsions and how they compare to other emulsion systems. Little research is available on dried nanoemulsions. The objectives of this research were to (i) study the effect of varying the continuous phase of nanoemulsions with different carbohydrate/protein ratios on subsequent emulsion stability, and (ii) compare the physicochemical properties, lactose crystallisation properties, microstructure, and lipid oxidation of spray dried nanoemulsions compared to spray dried conventional emulsions having different water and sugar contents. Nanoemulsions containing sunflower oil (10% w/w), β-casein (2.5–10% w/w) and lactose or trehalose (10–17.5%) were produced following optimisation of the continuous phase by maximising and minimising viscosity and glass transition temperature (Tg’) using mixture design software. Increasing levels of β-casein from caused a significant increase in viscosity, particle size, and nanoemulsion stability, while resulting in a decrease in Tg’. Powders were made from spray drying emulsions/nanoemulsions consisting of lactose or a 70:30 mixture of lactose:sucrose (23.9%), sodium caseinate (5.1%) and sunflower oil (11.5%) in water. Nanoemulsions, produced by microfluidisation (100 MPa), had higher stability and lower viscosity than control emulsions (homogenization at 17 MPa) with lower solvent extractable free fat in the resulting powder. Partial replacement of lactose with sucrose decreased Tg and delayed Tcr. DVS and PLM showed that in powdered nanoemulsions, lactose crystallises faster than in powdered conventional emulsions. Microstructure of both powders (CLSM and cryo-SEM) showed different FGS in powders and different structure post lactose crystallisation. Powdered nanoemulsions had lower pentanal and hexanal (indicators of lipid oxidation) after 24 months storage due to their lower free fat and porosity, measured using a validated GC HS-SPME method, This research has shown the effect of altering the continuous phase of nanoemulsions on microstructure of spray dried nanoemulsions, which affects physical properties, sugar crystallisation, and lipid oxidation.

Improving the care of preterm infants: before, during, and after, stabilisation in the delivery room

Introduction Up to 10% of infants require stabilisation during transition to extrauterine life. Enhanced monitoring of cardiorespiratory parameters during this time may improve stabilisation outcomes. In addition, technology may facilitate improved preparation for delivery room stabilisation as well as NICU procedures, through educational techniques. Aim To improve infant care 1) before birth via improved training, 2) during stabilisation via enhanced physiological monitoring and improved practice, and 3) after delivery, in the neonatal intensive care unit (NICU), via improved procedural care. Methods A multifaceted approach was utilised including; a combination of questionnaire based surveys, mannequin-based investigations, prospective observational investigations, and a randomised controlled trial involving preterm infants less than 32 weeks in the delivery room. Forms of technology utilised included; different types of mannequins including a CO2 producing mannequin, qualitative end tidal CO2 (EtCO2) detectors, a bespoke quantitative EtCO2 detector, and annotated videos of infant stabilisation as well as NICU procedures Results Manual ventilation improved with the use of EtCO2 detection, and was positively assessed by trainees. Quantitative EtCO2 detection in the delivery room is feasible, EtCO2 increased over the first 4 minutes of life in preterm infants, and EtCO2 was higher in preterm infants who were intubated. Current methods of heart rate assessment were found to be unreliable. Electrocardiography (ECG) application warrants further evaluation. Perfusion index (PI) monitoring utilised in the delivery room was feasible. Video recording technology was utilised in several ways. This technology has many potential benefits, including debriefing and coaching in procedural healthcare, and warrants further evaluation. Parents would welcome the introduction of webcams in the NICU. Conclusions I have evaluated new methods of improving infant care before, during, and after stabilisation in the DR. Specifically, I have developed novel educational tools to facilitate training, and evaluated EtCO2, PI, and ECG during infant stabilisation. I have identified barriers in using webcams in the NICU, to now be addressed prior to webcam implementation.

Organic Matter Removal from Piggery Wastewater in Waste Stabilisation Pond in Nigeria

Four (4) wastewater quality variables: chemical oxygen demand (COD), total solid (TS), total dissolved solid (TDS), and total suspended solid (TSS) were determined. Analysed samples comprises of raw influent and effluents entering and leaving the stabilisation ponds. Significant reduction in variables were obtained, maximum and minimum values obtained for COD were 917mg/l (anaerobic pond), and 13mg/l (maturation pond). For TS, TDS and TSS, maximum and minimum values obtained were 14,420mg/l, 9,180mg/l, 5,240mg/l and 3,398mg/l, 3,120mg/l, 278mg/l respectively. Removal efficiencies recorded for parameters in final effluent (maturation pond) were 98.55% (COD), 76.44% (TS), 66.01% (TDS), and 94.69% (TSS) respectively.

Développement d'un appareil médical pour la réduction et la stabilisation de fractures

Les méthodes d'opération permettant la stabilisation temporaire de fractures du fémur ont peu changé dans les dernières décennies. Ce mémoire illustre d'abord les différentes techniques chirurgicales présentement utilisées. Ces dernières sont principalement des outils manuels très simples. Un survol des recherches universitaires sur le sujet démontre que l'effort se porte principalement sur des manipulateurs robotisés complexes qui sont peu susceptibles d'être utilisés dans les salles d'opération à court terme. Avec l'aide de chirurgiens, il a été possible de connaître les besoins de ceux-ci en ce qui concerne la réduction et la stabilisation de fractures. Un appareil mécanique transparent à la radiographie a été conçu. Pour ce faire, plusieurs éléments de machine et mécanismes ont dû être développés en matériaux plastiques ou composites. L'appareil permet aux chirurgiens de déplacer un des fragments de l'os dans les six degrés de liberté puis de le maintenir stable. Un prototype a été fabriqué. Des essais avec un simulateur de fracture ont permis de récolter les commentaires de chirurgiens.

Uma perspectiva computacional sobre catálise enzimática

Enzymes are extremely efficient catalysts. Here, part of the mechanisms proposed to explain this catalytic power will be compared to quantitative experimental results and computer simulations. Influence of the enzymatic environment over species along the reaction coordinate will be analysed. Concepts of transition state stabilisation and reactant destabilisation will be confronted. Divided site model and near-attack conformation hypotheses will also be discussed. Molecular interactions such as covalent catalysis, general acid-base catalysis, electrostatics, entropic effects, steric hindrance, quantum and dynamical effects will also be analysed as sources of catalysis. Reaction mechanisms, in particular that catalysed by protein tyrosine phosphatases, illustrate the concepts.

The solution structure of the N-terminal zinc finger of GATA-1 reveals a specific binding face for the transcriptional co-factor FOG

Zinc fingers (ZnFs) are generally regarded as DNA-binding motifs. However, a number of recent reports have implicated particular ZnFs in the mediation of protein-protein interactions. The N-terminal ZnF of GATA-1 (NF) is one such finger, having been shown to interact with a number of other proteins, including the recently discovered transcriptional co-factor FOG. Here we solve the three-dimensional structure of the NF in solution using multidimensional H-1/N-15 NMR spectroscopy, and we use H-1/N-15 spin relation measurements to investigate its backbone dynamics. The structure consists of two distorted beta-hairpins and a single alpha-helix, and is similar to that of the C-terminal ZnF of chicken GATA-1. Comparisons of the NF structure with those of other C-4-type zinc binding motifs, including hormone receptor and LIM domains, also reveal substantial structural homology. Finally, we use the structure to map the spatial locations of NF residues shown by mutagenesis to be essential for FOG binding, and demonstrate that these residues all lie on a single face of the NE Notably, this face is well removed from the putative DNA-binding face of the NE an observation which is suggestive of simultaneous roles for the NF; that is, stabilisation of GATA-1 DNA complexes and recruitment of FOG to GATA-1-controlled promoter regions.

Frequency stabilised grating feedback laser diode for atom cooling applications

The free running linewidth of an external cavity grating feedback diode laser is on the order of a few megahertz and is limited by the mechanical and acoustic vibrations of the external cavity. Such frequency fluctuations can be removed by electronic feedback. We present a hybrid stabilisation technique that uses both a Fabry-Perot confocal cavity and an atomic resonance to achieve excellent short and long term frequency stability. The system has been shown to reduce the laser linewidth of an external cavity diode laser by an order of magnitude to 140 kHz, while limiting frequency excursions to 60 kHz relative to an absolute reference over periods of several hours. The scheme also presents a simple way to frequency offset two lasers many gigahertz apart which should find a use in atom cooling experiments, where hyperfine ground-state frequency separations are often required.

Effects of an oral vasopressin receptor antagonist (OPC-31260) in a dog with syndrome of inappropriate secretion of antidiuretic hormone

Objective The syndrome of inappropriate secretion of antidiuretic hormone is a rare disorder in dogs characterised by hypo-osmolality and persistent arginine vasopressin production in the absence of hypovolaemia and/or hypotension. The study describes the efficacy and safety of the nonpeptide selective arginine vasopressin V-2 receptor antagonist OPC-31260 in a dog with the naturally occurring syndrome. Design The detailed case history of a dog with spontaneous syndrome of inappropriate secretion of antidiuretic hormone that received long-term therapy with oral OPC-31260 is presented. Effects of the first dose of OPC-31260 and of a dose administered after a continuous dosing period of 12 days are reported. Procedure Packed cell volume, plasma sodium, total protein, arginine vasopressin, renin activity, atrial natriuretic peptide, urine specific gravity, urine output, heart rate and body weight were monitored for 2 h before, and for 4 h after, the first dose of OPC-31260. The same parameters plus plasma osmolality and urine osmolality were monitored when an identical dose was administered after 12 days of therapy. Results Oral administration of OPC-31260 at 3 mg/kg body weight resulted in marked aquaresis with increased urine output and decline in urine specific gravity within 1 h. Corresponding increases in concentrations of plasma sodium, plasma osmolality and plasma renin activity were recorded over a 4 h period. Arginine vasopressin concentration remained inappropriately elevated throughout the study. Results were similar when the trial procedure was repeated after a stabilisation period of 12 days. Long-term therapy with OPC-31260 at a dose of 3 mg/kg body weight orally every 12 h resulted in good control of clinical signs with no deleterious effects detected during a 3-year follow-up period. Despite sustained clinical benefits observed in this case, plasma sodium did not normalise with continued administration of the drug. Conclusions Treatment of a dog with naturally occurring syndrome of inappropriate secretion of antidiuretic hormone with OPC-31260 at 3 mg/kg body weight orally every 12 h resulted in marked aquaresis and significant palliation of clinical signs with no discernible side-effects detected over a 3-year period. Thus, OPC-31260 appears to offer a feasible medical alternative to water restriction for treatment of dogs with syndrome of inappropriate secretion of antidiuretic hormone. Higher doses of OPC-31260 may be required to achieve and maintain normal plasma sodium in dogs with this syndrome.

Statins withdrawal, vascular complications, rebound effect and similitude

Hahnemann considered the secondary action of medicines to be a law of nature and reviewed the conditions under which it occurs. It is closely related to the rebound effects observed with many modern drugs. I review the evidence of the rebound effect of statins that support the similitude principle. In view of their indications in primary and secondary prevention of cardiovascular diseases, statins are widely prescribed. Besides reducing cholesterol biosynthesis, they provide vasculoprotective effects (pleiotropic effects), including improvement of endothelial function, increased nitric oxide bioavailability, antioxidant properties, inhibition of inflammatory and thrombogenic responses, stabilisation of atherosclerotic plaques, and others. Recent studies suggest that suspension of statin treatment leads to a rebound imparing of vascular function, and increasing morbidity and mortality in patients with vascular diseases. Similarly to other classes of modern palliative drugs, this rebound effect is the same as a secondary action or vital reaction described by Samuel Hahnemann, and used in homeopathy in a therapeutic sense. Homeopathy (2010) 99, 255-262.

Contrasting Epstein-Barr virus-specific cytotoxic T cell responses to HLA A2-restricted epitopes in humans and HLA transgenic mice: implications for vaccine design

This study investigates the hierarchy of cytotoxic T cell (CTL) responses to twelve HLA A2-restricted epitopes from the latent, lytic and structural proteins of Epstein–Barr virus (EBV) in acute infectious mononucleosis and in healthy seropositive donors and the relative immunogenecity of these epitopes in transgenic mice. Responses to the lytic epitope were uniformly strong in all healthy seropositive individuals and acute infectious mononucleosis donors while moderate or low responses were observed to the latent and structural epitopes, respectively in both groups studied. In contrast, when HLA A2/Kb transgenic mice were immunised with these peptide epitopes, CTL responses were observed to all epitopes with a maximal response to the epitopes within the structural proteins and low to moderate responses to the latent epitopes. This hierarchy of CTL responses in mice was also reflected in an MHC stabilisation analysis. These contrasting CTL responses in humans following natural infection compared to the immunogenicity of these epitopes and their ability to stabilise MHC may need to be considered when designing an EBV vaccine.