Drug delivery systems based on sugar-macromolecule conjugates

The specificity of carbohydrate-protein interactions can greatly outstrip that of many other ligand-binding systems; such is the enormous density of information that sugars can convey. In addition, macromolecules allow for the fine-tuning of active drug delivery through their great ability to undergo site-specific modification and their inherent physicochemical properties. Once combined, these two factors suggest that sugar-macromolecule conjugates, targeted using endogenous carbohydrate binding proteins, are a promising route to the 'magic bullet'.     

Comparative pulmonary toxicity of blasting sand and five substitute abrasive blasting agents

Blasting sand is used for abrasive blasting, but its inhalation is associated with pulmonary inflammation and fibrosis. Consequently, safer substitute materials for blasting sand are needed. In a previous study from this laboratory, the comparative pulmonary toxicity of five abrasive blasting substitutes and blasting sand was reported. In this study, the pulmonary toxicity of blasting sand was compared to five additional abrasive blasting substitutes: steel grit, copper slag, nickel slag, crushed glass, and olivine. Exposed rats received by intratracheal instillation 10 mg of respirable-size particles of blasting sand or an abrasive blasting substitute, while controls were instilled with vehicle. Pulmonary inflammation, damage, and fibrosis were examined 28 d postexposure. Pulmonary inflammation was monitored by determining bronchoalveolar lavage polymorphonuclear cell counts and alveolar macrophage activation by chemiluminescence. Pulmonary damage was assessed by acellular bronchoalveolar (BAL) fluid serum albumin concentrations and lactate dehydrogenase activities. Histological examination of lung tissue samples was made to assess the severity and distribution of pulmonary fibrosis, alveolitis, and alveolar epithelial cell hypertrophy and hyperplasia. In comparison to blasting sand, olivine exposed rats had higher levels of pulmonary inflammation and damage with a similar level of fibrosis. Steel grit-exposed rats had lower levels of pulmonary inflammation and damage, and did not develop fibrosis. However, steel grit-exposed rats had a level of epithelial cell hypertrophy and hyperplasia similar to blasting sand. The other abrasive blasting substitutes gave a mixed profile of toxicity. The data demonstrate that steel grit produced less acute pulmonary toxicity than blasting sand or any of the other abrasive blasting substitutes. Notwithstanding, the data also suggest that chronic exposure to steel grit may pose a health risk due to its effects on epithelial cell proliferation in the lung.     

Effects of maternal separation on behavioural sensitization produced by repeated cocaine administration in adulthood

We examined whether early maternal separation influenced the susceptibility to behavioural sensitization produced by repeated intravenous (i.v.) injections of cocaine in adult female rats. For the first 21 days of life litters were separated from their mother for either 15 min (MS-15) or 180 min/day (MS-180). Control animals were subjected only to regular cage changes (animal facility reared; AFR). In adulthood, these three groups did not differ in their locomotor response to placement in a novel environment or to an acute i.v. injection of cocaine. After six additional daily injections of either saline or cocaine and following a 7-day drug-free interval, sensitization was assessed by giving all rats a challenge i.v. injection of cocaine. Rats exposed to either period of maternal separation (MS-15 or MS-180) showed significantly less robust sensitization than AFR rats. Therefore, early maternal separation decreased susceptibility to behavioural sensitization produced by cocaine in adulthood and the specific duration of maternal separation had no effect on this outcome.     

Polydispersity of a mammalian chaperone: mass spectrometry reveals the population of oligomers in alphaB-crystallin

The quaternary structure of the polydisperse mammalian chaperone alphaB-crystallin, a member of the small heat-shock protein family, has been investigated by using electrospray mass spectrometry. The intact assemblies give rise to mass spectra that are complicated by the overlapping of charge states from the different constituent oligomers. Therefore, to determine which oligomers are formed by this protein, tandem mass spectrometry experiments were performed. The spectra reveal a distribution, primarily of oligomers containing 24-33 subunits, the relative populations of which were quantified, to reveal a dominant species being composed of 28 subunits. Additionally, low levels of oligomers as small as 10-mers and as large as 40-mers were observed. Interpretation of the tandem mass spectral data was confirmed by simulating and summing spectra arising from the major individual oligomers. The ability of mass spectrometry to quantify the relative populations of particular oligomeric states also revealed that, contrary to the dimeric associations observed in other small heat-shock proteins, there is no evidence for any stable substructures of bovine alphaB-crystallin isolated from the lens.     

Desquamative gingivitis: a sign of mucocutaneous disorders--a review

Desquamative gingivitis is a clinical term to describe red, painful, glazed and friable gingivae which may be a manifestation of some mucocutaneous conditions such as lichen planus or the vesiculobullous disorders. It is important to be aware of this rare clinical entity so as to distinguish desquamative gingivitis from plaque induced gingivitis which is an extremely common condition, easily recognized and treated daily by the dental practitioner. This article gives an overview of desquamative gingivitis, its presentation, the possible causes, diagnosis and treatment. Early recognition of these lesions may prevent delayed diagnosis and inappropriate treatment of potentially serious dermatological diseases.