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Biomedical subjects

A Hoelgaard

Publications and source records attributed to A Hoelgaard.

9 recordsLinked to original sources

Serum growth hormone (GH) profiles after nasally administered GH in normal subjects and GH deficient patients.

OBJECTIVE: GH-deficient patients are at present treated with daily subcutaneous GH injections. Further improvements in patient compliance and effects of treatment may occur with nasal administration. We have examined the absorption of nasally administered GH in healthy subjects and in GH deficient patients in two separate studies. DESIGN: Healthy subjects and GH deficient patient were examined in the morning after an overnight fast. Twelve IU of GH in a powder containing didecanoyl-L-alpha-phosphatidylcholine as enhancer were administered in the nostrils (6 IU in each nostril) at the beginning of the study in the healthy subjects. The GH deficient subjects received a total of 6 IU GH/m2 intranasally. Blood was frequently sampled for up to 4 hours. Before and after nasal application anterior rhinoscopy was performed. PATIENTS: Eight normal subjects and 7 GH deficient patients. MEASUREMENTS: Serum GH. RESULTS: (mean +/- SD) Mean maximum concentration (Cmax) in the normal group was 57.6 mU/l +/- 36.9 with a mean time to obtain Cmax (Tmax) of 65 +/- 47 min. In the GH deficient group Cmax was 56.1 +/- 26.1 mU/l with a mean Tmax of 45 +/- 15 min. The subjects did not report any major inconvenience during the study. Anterior rhinoscopy did not reveal changes. CONCLUSION: Nasally administered GH is absorbed to a significant degree from the nasal mucosa without obvious untoward effects in the short term. These data encourage further studies with nasal GH administration.

Absorption↗

Patch testing with nickel chloride in a hydrogel.

Various concentrations of NiCl2 in a hydrogel were evaluated as a possible alternative to the standard patch test material of 5% NiSO4 pet. Patch test responses were recorded on a total of 430 patients with known or suspected contact allergy. A NiCl2 concentration of 1% or less in the hydrogel failed to elicit a response in some patients who reacted to 5% NiSO4 pet. The 2% NiCl2 hydrogel produced a small increase in response frequency and may reduce false-negative reactions. Along with the ability of the material to improve the topical bioavailability of nickel ions, more irritant reactions were observed. However, in cases with a positive history and a negative patch test with petrolatum, the hydrogel prepared from Methocel-E-4M seems to be a useful alternative vehicle for water-soluble allergens.

Dermatitis, Contact↗

Permeation of nickel through human skin in vitro--effect of vehicles.

The effect of the vehicle on the permeation rate of nickel ions through excised human skin was evaluated. Different hydrogels were compared with the standard patch test in petrolatum. A hydroxypropyl methylcellulose gel seemed to be the most promising alternative to petrolatum. It gave high bioavailability of the nickel and had good film forming properties leaving the nickel spread across the skin surface as a thin film without microscopically detectable crystals. The content of nickel in the various skin layers after cutaneous application was determined, and nickel was found to accumulate in the epidermis, probably due to epidermal binding. A significant amount of nickel was found also in the dermis. Occlusion and application of higher nickel concentrations increased the transport rate and must be considered in patch testing using this hydrogel. We conclude that nickel permeation is highly dependent of the choice of vehicle and the vehicle should, therefore, be an important consideration in patch testing with nickel.

Humans↗

Binding of nickel to human epidermis in vitro.

Human epidermis was homogenized, dried and incubated with nickel chloride solutions in the concentration range 0.008-3.4 mM/50 mg epidermis. Nickel uptake was found to occur according to the Freundlich adsorption isotherm, giving a slope of 0.55, indicating that nickel is associatively bound to constituents of the epidermis. The binding characteristics of cobalt were very similar to those of nickel, but the two metals were not found to compete significantly for binding sites in the epidermis. The metal-chelating agents, ethylenediamine tetra-acetic acid disodium, (Na-EDTA) L-histidine and D-penicillamine were tested for ability to remove nickel from its binding sites. Na-EDTA was found to be the most efficient, removing 70-90% of the nickel bound to the tissue. The possible clinical significance of these in vitro observations are discussed in relation to percutaneous absorption and allergic contact dermatitis.

Binding Sites↗

Permeation of nickel salts through human skin in vitro.

The impact of occlusion and the rôle of the counter ion on the permeation of nickel ions through skin have been examined using excised human skin. A highly sensitive electrochemical method was used to quantify the amount of nickel permeating the skin. The investigations show that nickel ions are capable of permeating the skin barrier when applied under occlusion. The process is slow, having a lag time of approximately 50 h. The permeation rate, and thus the physical amount being bioavailable, is considerably increased when aqueous nickel chloride is used in comparison with aqueous nickel sulphate. With respect to nickel permeation of the skin, we conclude that the choice of salt is an important consideration in patch testing.

Female↗

Adsorption of lecithin by cholesterol.

Egg lecithin was adsorbed significantly by cholesterol monohydrate crystals. Adsorption data obtained at initial concentrations of less than 1.1 mM lecithin fitted the Langmuir equation. The calculated adsorption capacity suggested formation of a lecithin bilayer or a mixed bilayer of lecithin and cholesterol. The amount of lecithin adsorbed was highly dependent on the cholate concentration in the incubation medium. Minimal adsorption was observed at approximately 5 mM cholate. The presence of quaternary ammonium slats and dioctyl sodium sulfosuccinate caused desorption. The finding of an adsorptive layer supported the existence of an interfacial barrier than controls cholesterol dissolution.

Adsorption↗