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Biomedical subjects

R Hyde

Publications and source records attributed to R Hyde.

12 recordsLinked to original sources

The effect of the uptake of particles on the chemotaxis of polymorphonuclear leucocytes in-vitro.

The relationship between the phagocytic uptake of latex microspheres (1.1 microns diam.) and the mobility of rat polymorphonuclear leucocytes (PMNLs) has been investigated in-vitro. The movement of PMNLs was found to be independent of the uptake of particles but about half of the PMNLs were not receptive to the chemo-attractant N-formylmethionyleucylphenylalanine. However, the uptake of particles was greater when particle/cell ratios were high and the greatest number of particles were carried into a cellulose nitrate filter by chemotaxis at the highest particle/cell ratio of 30:1.

Animals

The transport of microspheres from the gastro-intestinal tract to inflammatory air pouches in the rat.

The distribution of latex microspheres (1.1 microns diam) has been investigated in-vivo, as a potential passive targeted system for the treatment of inflammation. Microspheres administered orally were found in the circulation and in inflamed tissues and exudates of inflammatory air pouches in rats. Oral absorption was also found in a rabbit. Particles administered directly into the circulation also penetrated into the air pouch tissues and fluids. The possibility of using microspheres as a passive targeted system for the treatment of inflammation is discussed.

Administration, Oral

Analysis of structural requirements for the absorption of drugs and macromolecules from the nasal cavity.

An octapeptide and a protein, of molecular weights 800 and 34,000, respectively, were found to have nasal bioavailabilities of 73 and 0.6%, respectively, in the rat. This data, combined with reported values for 23 other compounds, indicated good availability without adjuvants for all molecules up to 1000 molecular weight (mean 70%, SD between compounds 26%, n = 15) with a decline in availability above this value. The relationship between absorption and molecular weight was modeled assuming competition between constant clearance from the nasal cavity and molecular weight-dependent transport through the mucosa. Deviations of absorption from values predicted by this model did not correlate with factors such as charge, hydrophobicity, or susceptibility to aminopeptidases, but the relative absorption of cyclic and cross-linked peptides and proteins was significantly greater than that of linear peptides. It is argued that the most likely route for transport is through junctions between cells and that surface-active adjuvants (MW 6000) which markedly enhance insulin uptake may act by rendering hydrophobic areas of contact of the junctional proteins temporarily hydrophilic. The nasal route is suitable for efficient, rapid delivery of many molecules of molecular weight less than 1000. With the use of adjuvants, this limit can be extended to at least 6000 and possibly much higher.

Absorption

Effects of sodium 5-methoxysalicylate on macromolecule absorption and mucosal morphology in a vascularly perfused rat gut preparation in vivo.

The effect of sodium 5-methoxysalicylate on absorption was assessed by measurement of the appearance of test compounds in the portal blood output of a perfused rat gut model. The test compounds were a hexapeptide analogue of somatostatin, insulin, and horseradish peroxidase. Considerable amounts of sodium 5-methoxysalicylate were present in the portal blood 10 min after intraduodenal administration. When co-administered with sodium 5-methoxysalicylate (60 mg), a marked increase in the concentrations of the test substances occurred at t = 15 min which lasted for a further 15 min. Quantities of less than 60 mg had much reduced adjuvant effects. In control experiments with no adjuvant, the concentrations of the test substances remained low throughout the 1-h period of blood collection. After the administration of 60 mg of sodium 5-methoxysalicylate, slight mucosal damage was apparent at 10 min. This became progressively worse with time and, at 1 h, extensive mucosal stripping had occurred. The results suggest, although they do not prove, that apparent adjuvant effects in the small intestine may be a direct consequence of serious mucosal damage. This means that care must be taken in the investigation of adjuvant properties to exclude the possibility that an observed increase in transport is due to gross loss of integrity of the membrane.

Animals

Induction of the hepatic mixed-function oxidases by Aroclor 1254 in the hamster: comparison of Aroclor-induced rat and hamster preparations in the activation of pre-carcinogens in the Ames test.

Hepatic microsomal mixed-function oxidase activities and the metabolic activation of chemical carcinogens to mutagens in the Ames test were investigated using Aroclor 1254-induced rat and hamster preparations. Benzphetamine N-demethylase, NADPH-cytochrome c reductase and cytochromes P-450 and b5 were induced in both animals to the same extent by pre-treatment with Aroclor. However, the O-deethylation of ethoxyresorufin was markedly induced in the rat (147-fold) but only modestly in the hamster (3-fold). 1,2-Benzanthracene and 4-aminobiphenyl were more efficiently activated by the rat preparations while, in contrast, 2-acetylaminofluorene, 2-aminoanthracene, nitrosopiperidine, nitrosopyrrolidine, cyclophosphamide and phenacetin were more efficiently activated by the hamster preparations. No significant difference was observed in the activation of 3-methylcholanthrene, benzo[a]pyrene and 2-aminofluorene. It is concluded that (a) the hamster is relatively refractive to cytochrome P-448 induction, and (b) Aroclor 1254-induced rat and hamster S9 preparations differ in their ability to convert chemical carcinogens to mutagens in the Ames test.

Animals

Intra-hospital transfer: effects on chronically ill psychogeriatric patients.

Since the Vermont State Hospital was approaching a major transition period, it was decided to study systematically the effects of intra-unit and inter-unit transfer on its psychogeriatric patients. Ten patients were assessed by means of four standardized measures in the intra-unit study, specifically investigating the effects of integrating wards previously devoted either to chronic or to acute psychiatric illness. Twenty-five patients from a specialized geriatric unit were evaluated, by separate investigators, with respect to changes occuring as a result of their transfer to regional mixed units. The critical incident log, the problem classification form, and the clinical global impression showed some changes, for which there were several possible explanations. None of the changes was as dramatic as predicted by staff members holding divergent views prior to the study. The optimists predicted a "blossoming" of the psychogeriatric patients in the mixed, regional units, whereas the pessimists prophesied dire consequences. The group of patients studied was not completely homogeneous with respect to the effect to transfer. Clinical assessment after transfer could be relied on to detect improvement in some of these psychogeriatric patients and deterioration in others. Some understanding of the complexity of the multifactor determinants of change developed along with increased cooperation among the investigators and the nursing staff. A middle ground of mutual respect for fresh ideas and an appreciation for years of experience was reached.

Acute Disease