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Biomedical subjects

Robert Webster

Publications and source records attributed to Robert Webster.

8 recordsLinked to original sources
PubMed2006

Application of centrifugation to the large-scale purification of electric arc-produced single-walled carbon nanotubes.

We report a further advance in the bulk purification of nitric acid-treated single-walled carbon nanotubes (SWNTs) by use of high-speed centrifugation. We have already shown that low-speed centrifugation is effective in removing amorphous carbon (AC). In these earlier experiments, the AC preferentially suspends in aqueous dispersions on low-speed centrifugation (2000g), leaving the SWNTs in the sediment. In a surprising reversal, we now show that high-speed centrifugation (20000g) of well-dispersed preparations is effective in sedimenting carbon nanoparticles (CNP), while leaving the SWNTs suspended in aqueous media. Taken together, these two techniques allow the bulk scale (10 g) purification of SWNTs by efficiently separating the two main contaminants, in an industrially viable process. We show that the mechanism of these separations is based on the differential charging (zeta-potential) of the AC, CNPs, and SWNTs that comes about during the chemical processing. Due to their more robust structure, nitric acid oxidation leaves the CNPs with a surface charge density lower than that of the SWNTs, and thus the CNPs do not form stable dispersions in aqueous media during high-speed centrifugation. The efficiency of the process was confirmed by the high purification recovery factor (PRF = 90%), which is a measure of the fractional quantity of the product recovered after the purification. We demonstrate that the purity of SWNTs significantly affects their mechanical and electrical properties.

Journal Article↗
PubMed2005

Receptor specificity of influenza viruses from birds and mammals: new data on involvement of the inner fragments of the carbohydrate chain.

We studied receptor-binding properties of influenza virus isolates from birds and mammals using polymeric conjugates of sialooligosaccharides terminated with common Neu5Ac alpha2-3Gal beta fragment but differing by the structure of the inner part of carbohydrate chain. Viruses isolated from distinct avian species differed by their recognition of the inner part of oligosaccharide receptor. Duck viruses displayed high affinity for receptors having beta1-3 rather than beta1-4 linkage between Neu5Ac alpha2-3Gal-disaccharide and penultimate N-acetylhexosamine residue. Fucose and sulfate substituents at this residue had negative and low effect, respectively, on saccharide binding to duck viruses. By contrast, gull viruses preferentially bound to receptors bearing fucose at N-acetylglucosamine residue, whereas chicken and mammalian viruses demonstrated increased affinity for oligosaccharides that harbored sulfo group at position 6 of (beta1-4)-linked GlcNAc. These data suggest that although all avian influenza viruses preferentially bind to Neu5Ac alpha2-3Gal-terminated receptors, the fine receptor specificity of the viruses varies depending on the avian species. Further studies are required to determine whether observed host-dependent differences in the receptor specificity of avian viruses can affect their ability to infect humans.

Animals↗
PubMed2004

Molecular constraints to interspecies transmission of viral pathogens.

The successful replication of a viral pathogen in a host is a complex process involving many interactions. These interactions develop from the coevolution of pathogen and host and often lead to a species specificity of the virus that can make interspecies transmissions difficult. Nevertheless, viruses do sporadically cross species barriers into other host populations, including humans. In zoonotic infections, many of these interspecies transfer events are dead end, where transmission is confined only to the animal-to-human route but sometimes viruses adapt to enable spread from human to human. A pathogen must overcome many hurdles to replicate successfully in a foreign host. The viral pathogen must enter the host cell, replicate with the assistance of host factors, evade inhibitory host products, exit the first cell and move on to the next, and possibly leave the initial host and transmit to another. Each of these stages may require adaptive changes in the pathogen. Although the factors that influence each stage of the replication and transmission of most agents have not been resolved, the genomics of both hosts and pathogens are now at hand and we have begun to understand some of the molecular changes that enable some viruses to adapt to a new host.

Animals↗
PubMed2004

Recurrent superior oblique myokymia in a patient with retinitis pigmentosa.

Superior oblique myokymia is an infrequently encountered condition, presenting with episodes of oscillopsia and/or vertical or oblique nystagmus, accompanied by a fine, monocular, cyclorotational nystagmus. Recent research suggests it is caused by vascular compression of the trunk of the trochlear nerve. The clinical features of a patient reporting three episodes of superior oblique myokymia, each following childbirth, are described. She had previously been diagnosed with retinitis pigmentosa. The possible aetiologies of superior oblique myokymia are described and appropriate assessment and possible referral for further testing detailed.

Adult↗
PubMed2003

Design of ester prodrugs to enhance oral absorption of poorly permeable compounds: challenges to the discovery scientist.

Many drugs are administered at sites that are remote from their site of action. The most common route of drug delivery is the oral route. The optimal physicochemical properties to allow high transcellular absorption following oral administration are well established and include a limit on molecular size, hydrogen bonding potential and adequate lipophilicity. For many drug targets, synthetic strategies can be devised to balance the physicochemical properties required for high transcellular absorption and the SAR for the drug target. However, there are drug targets where the SAR requires properties at odds with good membrane permeability. These include a requirement for significant polarity and groups that exhibit high hydrogen bonding potential such as carboxylic acids and alcohols. In such cases, prodrug strategies have been employed. The rationale behind the prodrug strategy is to introduce lipophilicity and mask hydrogen bonding groups of an active compound by the addition of another moiety, most commonly an ester. An ideal ester prodrug should exhibit the following properties: 1). Weak (or no) activity against any pharmacological target, 2). Chemical stability across a pH range, 3). High aqueous solubility, 4). Good transcellular absorption, 5). Resistance to hydrolysis during the absorption phase, 6). Rapid and quantitative breakdown to yield high circulating concentrations of the active component post absorption. This paper will review the literature around marketed prodrugs and determine the most appropriate prodrug characteristics. In addition, it will examine potential Discovery approaches to optimising prodrug delivery and recommend a strategy for prosecuting an oral prodrug approach.

Administration, Oral↗