External signal-activated liposomal drug delivery systems

Modern drug discovery gives rise to a great number of potential new therapeutic agents, but in some cases the efficient treatment of patient may not be achieved because the delivery of active compounds to the target site is insufficient. Thus, drug delivery is one of the major challenges in current pharmaceutical research. Numerous nanoparticle-based drug carriers, e.g. liposomes, have been developed for enhanced drug delivery and targeting. Drug targeting may enhance the efficiency of the treatment and, importantly, reduce unwanted side effects by decreasing drug distribution to non-target tissues. Liposomes are biocompatible lipid-based carriers that have been studied for drug delivery during the last 40 years. They can be functionalized with targeting ligands and sensing materials for triggered activation. In this study, various external signal-assisted liposomal delivery systems were developed. Signals can be used to modulate drug permeation or release from the liposome formulation, and they provide accurate control of time, place and rate of activation. The study involved three types of signals that were used to trigger drug permeation and release: electricity, heat and light. Electrical stimulus was utilized to enhance the permeation of liposomal DNA across the skin. Liposome/DNA complex-mediated transfections were performed in tight rat epidermal cell model. Various transfection media and current intensities were tested, and transfection efficiency was evaluated non-invasively by monitoring the concentration of secreted reporter protein in cell culture medium. Liposome/DNA complexes produced gene expression, but electrical stimulus did not enhance the transfection efficiency significantly. Heat-sensitive liposomal drug delivery system was developed by coating liposomes with biodegradable and thermosensitive poly(N-(2-hydroxypropyl) methacrylamide-mono/dilactate polymer. Temperature-triggered liposome aggregation and contents release from liposomes were evaluated. The cloud point temperature (CP) of the polymer was set to 42 °C. Polymer-coated liposome aggregation and contents release were observed above CP of the polymer, while non-coated liposomes remained intact. Polymer precipitates above its CP and interacts with liposomal bilayers. It is likely that this induces permeabilization of the liposomal membrane and contents release. Light-sensitivity was introduced to liposomes by incorporation of small (< 5 nm) gold nanoparticles. Hydrophobic and hydrophilic gold nanoparticles were embedded in thermosensitive liposomes, and contents release was investigated upon UV light exposure. UV light-induced lipid phase transitions were examined with small angle X-ray scattering, and light-triggered contents release was shown also in human retinal pigment epithelial cell line. Gold nanoparticles absorb light energy and transfer it into heat, which induces phase transitions in liposomes and triggers the contents release. In conclusion, external signal-activated liposomes offer an advanced platform for numerous applications in drug delivery, particularly in the localized drug delivery. Drug release may be localized to the target site with triggering stimulus that results in better therapeutic response and less adverse effects. Triggering signal and mechanism of activation can be selected according to a specific application.

Protein turnover in malnourished patients with cystic fibrosis: Effects of elemental and nonelemental nutritional supplements

To evaluate the relative efficacy of nonele-mental versus semielemental enteral supplements for nutritional rehabilitation of cystic fibrosis (CF) patients, whole-body protein turnover using the [15N]glycine method was studied in nine malnourished CF patients during enteral feedings, in a block design study compar-ing a semielemental formula (Criticare), a higher protein density but nonelemental formula (Traumacal) (T), and a nonelemental formula that had been modified to become isocaloric and isonitrogenous to the semielemental formula (modified Traumacal, MT). No significant differences in rates of protein synthesis or catabolism were observed comparing the three formulas. However the higher protein density nonelemental formula resulted in higher net protein deposition compared to the other two formulas (T + 0.42 g kg-110 h-1versus 0.33 g kg-110 h-1for Criticare and-0.59 g kg-110 h-1for MT), although this was significant (p < 0.05) for the MT versus T comparison only. This study lends support to the use of less expensive nonelemental formulas for the nutritional management of malnourished patients with CF. © 1990 Raven Press Ltd, New York.

Photo-​induced proton coupled electron transfer from a benzophenone 'antenna' to an isoindoline nitroxide

The current study reports the synthesis and properties of a novel isoindoline nitroxide contg. a benzophenone chromophore fused into the carbon framework. When exposed to UV light, rather than undergoing traditional benzophenone photochem. pathways, the presence of the nitroxide enables an energy transfer process whereby the nitroxide enters an excited state which induces an efficient hydrogen atom transfer from unactivated alkanes.

Use of narrow-pore filters in He II transfer devices - new results

With the aim of finding simple methods for the fabrication of He II refilling devices, He II flow has been studied through filters made from various fine powders (oxides and metals, grain sizes in the range 0.05–2 μm) by compacting them under pressure. The results obtained for the different states of He II flow, especially in the “breakthrough” and “easy flow” range, are explained by the fountain effect, He II hydrodynamics and the choking effect. According to the results, pressedpowder filters can be classified into three groups with different flow characteristics, of which the “good transfer filters” with a behaviour neatly described by simple theory are suitable for use in He II refilling devices.

A 1h And 13c Magnetic Resonance And Infrared Spectroscopic Study Of Coordinated 2-Aminocyclopentene-1-Dithiocarboxylic Acid And Its S-Methyl Ester

The ligating properties of 2-aminocyclopentene-1-dithiocarboxylic acid and its S-methyl esters were investigated. Complexes with Zn(II), Cd(II) and Hg(II) halides were synthesized and characterized by infrared and proton and carbon-13 NMR studies. The results are concordant with a bidentate coordination of the -CS2 group to the metal ions

Compressible second-order boundary layers for three-dimensional stagnation point flows with mass transfer

All the second-order boundary-layer effects have been studied for the steady laminar compressible 3-dimensional stagnation-point flows with variable properties and mass transfer for both saddle and nodal point regions. The governing equations have been solved numerically using an implicit finite-difference scheme. Results for the heat transfer and skin friction have been obtained for several values of the mass-transfer rate, wall temperature, and also for several values of parameters characterizing the nature of stagnation point and variable gas properties. The second-order effects on the heat transfer and skin friction at the wall are found to be significant and at large injection rates, they dominate over the results of the first-order boundary layer, but the effect of large suction is just the opposite. In general, the second-order effects are more pronounced in the saddle-point region than in the nodal-point region. The overall heat-transfer rate for the 3-dimensional flows is found to be more than that of the 2-dimensional flows.

Intra and Inter-Molecular Communications Through Protein Structure Network

Communication within and across proteins is crucial for the biological functioning of proteins. Experiments such as mutational studies on proteins provide important information on the amino acids, which are crucial for their function. However, the protein structures are complex and it is unlikely that the entire responsibility of the function rests on only a few amino acids. A large fraction of the protein is expected to participate in its function at some level or other. Thus, it is relevant to consider the protein structures as a completely connected network and then deduce the properties, which are related to the global network features. In this direction, our laboratory has been engaged in representing the protein structure as a network of non-covalent connections and we have investigated a variety of problems in structural biology, such as the identification of functional and folding clusters, determinants of quaternary association and characterization of the network properties of protein structures. We have also addressed a few important issues related to protein dynamics, such as the process of oligomerization in multimers, mechanism on protein folding, and ligand induced communications (allosteric effect). In this review we highlight some of the investigations which we have carried out in the recent past. A review on protein structure graphs was presented earlier, in which the focus was on the graphs and graph spectral properties and their implementation in the study of protein structure graphs/networks (PSN). In this article, we briefly summarize the relevant parts of the methodology and the focus is on the advancement brought out in the understanding of protein structure-function relationships through structure networks. The investigations of structural/biological problems are divided into two parts, in which the first part deals with the analysis of PSNs based on static structures obtained from x-ray crystallography. The second part highlights the changes in the network, associated with biological functions, which are deduced from the network analysis on the structures obtained from molecular dynamics simulations.

Heat transfer in a MHD flow between eccentric disks rotating at different speeds

Heat transfer in a MHD flow between two infinite eccentric disks rotating with different speeds is considered when the plates are maintained at different temperatures. The results for the corresponding nonmagnetic case presented wrongly by Banerjee and Borkakati [7] are corrected. It is observed that the eccentric rotation reduces the heat transfer on the disks.

Cloning Of Rice Dna And Identification Of Transfer-Rna Gene Clones

THE rapid development of recombinant DNA technology has brought forth a revolution in biology'>", it aids us to have a closer look at the 'way genes are organized, eS11 ecially in the complex eucaryotic genornes'<", Although many animal and yeast genes have been studied in detail using recombinant DNA technology, plant genes have seldom been targets for such studie., Germination is an ideal process to study gene expression .because it effects a . shift in the metabolic status of seeds from a state of 'dormancy to an active one. AJ;l understanding of gene organization and regulation darin.g germination can be accomplblted by molecular cloning of DNA from seeds lik.e rice. To study the status of histone, rRNA tRNA and other genes in the rice genome, a general method was developed to clone eucarvotic DNA in a' plasmid vector pBR 322. This essentially ~ involves the following steps. The rice embryo and plasmid pBR 322 DNAs were cut witll restriction endonuclease Bam Hi to generate stick.Y ends, The plasmid DNA was puosphatased, the DNA~ ware a~·tnealed and joined 'by T4 phage DNA ligase. The recombinant DNA molecules thus produced were transjerred into E. coli and colonies containing them Were selected by their sensitivity to tetracycline and resistance to ampicillin, Two clones were identified . 2S haVing tRNA genes by hybridization of the DNA in the clones \vitl1 32P-la.belled rice tRNAs.

Vaccination with an Insulin-like Growth Factor Binding Protein-1 (IGFBP-1)-bBased Vaccine Improves Growth in Feed-Restricted Brahman Steers

Dry-season weight loss in grazing cattle in northern Australia has been attenuated using a number of strategies (Hunter and Vercoe, 1987, Sillence et al. 1993, Gazzola and Hunter, 1999). Furthermore, the potential to improve efficiency of feed utilisation (and thus, dry-season performance) in ruminants through conventional modulation of the insulin-like growth factor (IGF) axis (Oddy and Owens, 1997, Hill et al., 1999) and through immunomodulation of the IGF axis (Hill et al., 1998a,b) has been demonstrated. The present study investigated the use of a vaccine directed against IGFBP-1 in Brahman steers which underwent a period of nutritional restriction followed by a return to wet-season grazing.

Fibre Transfer in Merino Ewes Mated with Damara, Merino or Dorper Rams in Central Western Queensland

Considerable concern has been expressed by the Australian wool industry regarding the contamination of the clip with coloured or kempy fibres from imported breeds of sheep. As part of the evaluation of imported sheep meat breeds in western Queensland, a study is examining fibre growth and transfer of fibres and the potential to cause physical contamination of Merino fleeces. The breeds of concern in this study are the Damara, a fat-tailed breed with a hairy, coloured fleece and the Dorper which has both pigmented fibres and a kempy fleece which is shed cyclically. Three groups of Merino 27 ewes were mated to Merino, Damara and Dorper rams respectively and fibre transfer to the Merino ewes during mating, from lambing to weaning and during grazing, assessed. Both a direct field method and a laboratory method (Hatcher 1995) are being used. Those measured by direct count were measured immediately after joining and 2, 4 and 8 weeks subsequently. and the other ewes were shorn and sampled and measured in the laboratory using the dark fibre detector. This paper presents preliminary findings of those ewes monitored by the direct field method. Animal production for a consuming world : proceedings of 9th Congress of the Asian-Australasian Association of Animal Production Societies [AAAP] and 23rd Biennial Conference of the Australian Society of Animal Production [ASAP] and 17th Annual Symposium of the University of Sydney, Dairy Research Foundation, [DRF]. 2-7 July 2000, Sydney, Australia.

Boundary-layer convective heat transfer in a convergent channel

In this paper the numerical solution of the heat transfer problem in a convergent channel with uniform and non-uniform wall temperatures under boundary-layer approximations has been presented. Also, a semi-analytical solution for uniform wall temperature has been obtained.