Permeability of human epidermis to phenolic compounds.
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Biomedical subjects
Publications and source records attributed to M S Roberts.
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The effects of interactions between drug and skin, drug and vehicle, and vehicle and skin on the overall penetration rate of a drug through the skin may be evaluated by comparison of penetration rates through excised skin and an inert reference membrane such as polyethylene. Dimethyl sulphoxide, dimethyl formamide, ethanol and water increase the permeability of the skin but because of reduced thermodynamic activities in the vehicles low penetration rates are observed.
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Two types of human IgA myeloma proteins were distinguished by immunochemical tests. Seven of 51 IgA-myeloma proteins contained an an tigenic determinant that was not de tected in the other 44 proteins. The distinctive antigenic site was not dem onstrated on either the heavy or light polypeptide chains.
Previous studies from this laboratory indicated infection of dendritic cells (DC) from peripheral blood of individuals infected with HIV1. Here, further evidence for the infection of peripheral blood DC with HIV1 is presented. Low-density cells (LDC) were prepared from blood mononuclear cells of HIV-infected individuals at different clinical stages of disease. These cells are enriched (10-40%) for MHC class-II-bearing DC, while most of the remaining cells are monocytes, and 2-10% are lymphocytes. A quantitative polymerase chain technique (PCR) was used to estimate the HIV provirus load in LDC and lymphocytes of patients in different disease categories. HIV provirus was detected in every LDC preparation, and for many individuals, particularly CDC stage IV patients, the load was higher in the LDC than in the lymphocyte fraction. These findings suggested that patient DC are infected with HIV. In order to provide confirmatory evidence for this conclusion, PCR was performed on DC that were highly purified from LDC by panning to remove contaminating T, B, natural killer and monocytic cells. High levels of HIV provirus were found in these purified DC. These findings suggest that DC provide a reservoir of HIV and that the consequences of such infection may be relevant to the development of disease.
Nifedipine has been reported to aggravate symptoms of ischaemic heart disease in some patients. To investigate the possible reasons for this, vascular resistance changes in the systemic and coronary beds of sheep were compared with and without coronary artery stenoses. In six anaesthetized sheep, the dose-response curve comparing vascular resistance to nifedipine dose showed greater sensitivity than that reported for either dogs or humans. The coronary vascular bed was more reactive than the systemic vascular bed but this difference did not reach a level of statistical significance. With fixed non-elastic proximal coronary artery stenoses, the relationship of both coronary flow and coronary resistance to a standard dose of nifedipine (5 micrograms/kg) was indirectly related to the degree of stenosis. With stenosis reducing flow at rest by 50% or more, nifedipine usually produced a reduction in coronary flow in the stenosed artery and associated ST elevation, consistent with severe ischaemia in the distribution of the coronary. This effect is related to the reduction in perfusion pressure.
A miniature fiber optic spectrometer enclosed within a semipermeable (dialysis) membrane is proposed for in vivo interstitial sensing applications. The semipermeable membrane acts as a molecular filter, allowing only small molecules to pass through to the sampling volume. This filtering, in principle, should enable continuous in vivo drug sensing, removing the necessity for complex microdialysis systems. We use a biological phantom to examine the reliable detection of a fluorescence signal from small dye molecules in the presence of large fluorophores and scatterers. We find that spectral artefacts arising from scatterers and large fluorophores are substantially suppressed, simplifying the spectral analysis. In addition, the measured sampling rate of 157 s is superior to existing in vivo tissue assaying techniques such as microdialysis, which can take tens of minutes.
The reservoir function of the skin is an important determinant of the duration of action of a topical solute. The reservoir can exist in the stratum corneum, in the viable avascular tissue (viable epidermis and supracapillary dermis) and in the dermis. A steroid reservoir in the stratum corneum has been demonstrated by the reactivation of a vasoconstrictor effect by occlusion or application of a placebo cream to the skin some time after the original topical application of steroid. Other solutes have also been reported to show a reservoir effect in the skin after topical application. A simple compartmental model is used to understand why reactivation of vasoconstriction some time after a topical steroid application shows dependency on time, topical solute concentration and the product used to cause reactivation. The model is also used to show which solutes are likely to show a reservoir effect and could be potentially affected by desquamation, especially when the turnover of the skin is abnormally rapid. A similar form of the model can be used to understand the promotion of reservoir function in the viable tissue and in the dermis in terms of effective removal by blood perfusing the tissues.
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