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Biomedical subjects

S Gizurarson

Publications and source records attributed to S Gizurarson.

24 records · Page 2Linked to original sources

The effect of cholera toxin and cholera toxin B subunit on the nasal mucosal membrane.

The effects of the self-adjuvanting substances, cholera toxin (CT) and cholera toxin B subunit (CTB), on rabbit nasal mucosal membrane, were investigated by using Ussing chambers. The control nasal mucosa (lateral wall), isolated from rabbits and mounted in the chamber, showed transepithelial potential difference, short-circuit current and conductance of -10 mV, 200 microA cm-2 and 20 mS cm-2, respectively. These parameters were compared with mucosa isolated from human inferior conchae, showing that rabbit nasal mucosa may be usable to understand effects on human mucosa. When the mucosa was exposed to various concentrations of CTB and CT, the short-circuit current and conductance of the mucosa increased with increasing concentration. CTB showed gradual increase in the short-circuit current when added in the same molar concentration as the B subunit contained in CT, which caused drastic changes by increasing the current to infinite value. Furthermore, the total amount of transepithelially fluxed CTB, which occurred rapidly after addition to the mucosal side of the chambers, increased with increasing CTB concentration. On the other hand, less flux was observed after addition of CT. These changes could be blocked by addition of ganglioside GM1. This demonstrates that the effect of CTB on the rabbit mucosal membrane are different from those of CT, although both CT and CTB act specifically on the membrane via the CTB receptor, ganglioside GM1.

Adenylyl Cyclases↗

Estimating tissue permeability and other bioelectrical parameters using membrane voltage and short-circuit current.

Evaluating the acute toxic effects of drugs or toxins is based mainly on studies which require the use of light microscopy. Recently, the effects of such substances on biological membranes, such as the nasal membrane, has been studied using the traditional Ussing chambers, which make it possible to study the transepithelial flux of drugs across membranes and to measure some bioelectrical parameters. A model is described, with which the changes in the membrane permeability, for sodium, potassium and chlorine, can be calculated directly, based on values obtained from the Ussing chamber system. Also, an experiment is described for evaluating the toxic effects of the cholera toxin B subunit, by measuring these changes in isolated rabbit nasal mucosa.

Animals↗

Insulin-carrying microspheres, in vitro studies.

Loading and release characteristics of insulin-carrying albumin and starch microspheres have been studied in vitro. The sorption characteristics of 125I-labelled insulin onto albumin microspheres were studied and were found to be completed within 5h, and the loading capacity was found to be 0.14% w/w. Insulin did not show any sorption into the matrix of the starch microspheres. The release characteristics were analyzed by high performance liquid chromatography. About 80% was released within 5-10 min from albumin microspheres and starch microspheres, respectively.

Humans↗

Study of nasal enzyme activity towards insulin. In vitro.

The possibility of insulin being enzymatically degraded in contact with the nasal mucosa has been studied in vitro. The insulin concentration was followed during 3 h incubation at 37 degrees C with freshly collected human nasal wash, isolated enzymes from pig and rabbit nasal mucosal tissue, leucine aminopeptidase and microsomal aminopeptidase, respectively. The rate of degradation with human nasal wash was found to be less than or equal to 0.02 microgram/min, which indicates that less than 0.5% of an intranasally applied insulin dose may be destroyed by local enzymes during the time of absorption. The observed degradation was not found to be limiting for an intranasal application of insulin.

Administration, Intranasal↗

Animal models for intranasal drug delivery studies. A review article.

The purpose of this review is to introduce the investigators to sources of information and to guiding principles regarding the choice of animal models for experimental and clinical studies on intranasal application studies. It focuses also on the anatomical and physiological variations that can influence the selection of the correct animal model. A topical overview is given for following animal models which are all involved in intranasal drug or vaccine delivery research; dog, guinea pig, hamster, mouse, rabbit (in vivo and in situ), rat (in vivo, in vivo surgical and in situ) and sheep. In the selection of an animal model, both advantages and disadvantages must be considered. Small animals such as guinea pigs, hamsters, mice and rats, are easy to handle and inexpensive, but their nasal cavity is small and therefore preferred for absorption studies and for studying the influence of absorption promoters. Dogs, monkeys, sheep and rabbits are particularly useful in pharmacokinetic and formulation studies.

Administration, Intranasal↗

A simple flow injection analysis for studies of drug-protein binding interactions in serum.

Studies of drug-protein binding constants (ka) and of the degree of binding (%B) in biological fluids have been carried out by means of flow injection analysis (FIA). The association constants found for clinically relevant concentrations agree with the literature data. The degree of binding found for discoumarol, phenytoin and sulfisoxazole is also in agreement with the literature whereas that of warfarin is slightly lower.

Blood Proteins↗