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Biomedical subjects

J Sjögren

Publications and source records attributed to J Sjögren.

At least 19 recordsLinked to original sources

Androgen hormone binding to adipose tissue in rats.

Nuclear binding of androgen was examined, using R 1881, a synthetic androgen. The amount of androgen-receptor complexes bound to isolated nuclei was determined in isolated adipocytes from the epididymal (Epi), retroperitoneal (Ret), inguinal (Ing) and mesenteric (Mes) adipose tissues from intact and castrated rats. The binding was specific and saturable with a Kd in the nanomolar range. Binding was examined after 2 days and after 1 and 2 weeks after castration, showing a higher binding in the Mes tissue in comparison with Ing at all time-points (P < 0.05). Mes adipocytes showed a trend (0.05 < P < 0.1) to up-regulate their binding capacity 2 days after castration, and a significant (P < 0.05) downregulation 2 weeks after castration. Two days after castration, R 1881 binding, expressed per mg triacylglycerol (TG), was generally higher in the Mes region (P < 0.05). This was not fully significant in comparison with Epi tissue in intact rats. When expressed per cell the differences were somewhat diminished, due to differences in cell sizes. Androgen binding showed a negative correlation with TG-uptake in vivo (r = 0.85, P < 0.01), suggesting that a higher density of androgen receptors leads to a more inhibited lipid uptake. In conclusion, a specific androgen receptor was demonstrated in adipose tissue in rat, showing regional differences and a negative correlation with the lipid accumulation of the tissue.

Adipose Tissue

Glucocorticoid hormone binding to rat adipocytes.

Previous quantification of glucocorticoid receptor (GR) binding in adipose tissue has been performed in cytosol preparations, which did not allow the determination of the total number of GR in the cell. Therefore, GR binding was determined in intact adipocytes. Dexamethasone (dex) was used as a ligand in adipocytes isolated from epididymal (Epi), retroperitoneal (Ret), inguinal (Ing) and mesenteric (Mes) adipose tissue regions in male rats. The binding was saturable and specific with a Kd in the nanomolar range, not different from previously reported affinity of binding in cytosol preparations from adipocytes. Binding capacity rose after removal of endogenous glucocorticoids either by adrenalectomy (ADX) or culture in a glucocorticoid-free medium. Binding capacity of adipocytes was in general higher in Mes adipose cells than in adipocytes from Epi, Ing and Ret tissues from intact and ADX animals when expressed per unit of triglyceride weight of adipose tissues. This seemed to be largely explainable by a higher cellular density in Mes than in other adipose tissues. When comparisons were performed with binding per adipocyte, intraabdominal (Epi, Ret and Mes) cells bound more dex than adipocytes from subcutaneous (Ing) adipose tissue. It is suggested that in comparison with other adipose tissues Mes tissue has a higher density of the GR in situ, due mainly to a higher cellular density. Intraabdominal adipocytes in general seem to have a higher GR density than subcutaneous cells. This might explain the high activity of glucocorticoid-regulated metabolic pathways in intraabdominal particularly Mes adipose tissue.

Adipocytes

Design of a new multiple-unit controlled-release formulation of metoprolol--metoprolol CR.

A new controlled-release (CR) formulation of the beta 1-selective adrenoceptor antagonist metoprolol has been developed, aiming at an even 24-h pharmacological effect. In order to achieve this, using a once-daily dose, factors such as absorption characteristics, physicochemical properties, and technological aspects had to be considered. The new formulation, called metoprolol CR, is a disintegrating tablet consisting of several hundred coated pellets of metoprolol succinate, each pellet being its own CR delivery unit. In vitro testing and in vivo studies in healthy volunteers show that the new CR formulation gives continuous delivery of metoprolol throughout the day, resulting in smooth plasma concentration profiles, without peaks and troughs. The release of the drug is independent of pH and other physiological variables, such as food intake, which do not seem to alter the biopharmaceutical properties of the formulation.

Delayed-Action Preparations

Force-displacement measurements in tableting.

The influence of particle interaction, i.e. friction and bonding, on the net work (NETW) during compaction and on Heckel plots was tested by varying the particle size, the lubrication or the moisture content. The NETW was found to be significantly affected by particle interaction. The yield pressure, calculated from Heckel plots, was far less dependent on particle interaction and appears to be more useful for the evaluation of the deformation properties of materials. The NETW may be useful as a test of inter-lot variations in compaction behaviour of materials, due to its high sensitivity to both inter- and intraparticle properties, good reproducibility and low dependence upon die wall conditions. However, it appears to be a poor measure of the plastic properties of the substance.

Chemistry, Pharmaceutical

Work of friction and net work during compaction.

Series of tablets were compressed in a reciprocating tablet machine with a gradually increasing die wall friction. The force needed on the upper punch to maintain the tablet dimensions constant increased with the die wall friction while the lower punch force decreased. The change in punch forces due to differences in die wall friction had no effect on the tablet strength. The net work of compaction should be constant under these circumstances. The net work calculated by subtracting the work of friction and the expansion work from the gross work input was constant when the frictional work was calculated according to one of the two equations proposed in the literature (Järvinen & Juslin 1974) while the other appears to give an overestimation of the work of friction.

Tablets

Pharmacokinetics of procainamide intravenously and orally as conventional and slow-release tablets.

Pharmacokinetics of procainamide were studied in healthy volunteers after single doses intravenously and orally as conventional and slow-release tablets and after repeated oral doses to steady state. The initial distribution after intravenous administration was rapid and the overall elimination in the beta-phase corresponded to t1/2 of 2.7 hr. The mean volume of the central compartment was small and only 4 percent of V-d (beta), which was 2.3 l/kg body weight. About 65 percent was excreted unchanged after intravenous administration and about 55 percent after a single oral dose of 500 mg. The recovery of the metabolite N-acetylprocainamide was 12 percent after both routes of administration. Procainamide was completely absorbed from the gastrointestinal tract and the first-pass elimination was very limited. The rates of absorption from the tablet compositions were well correlated to the in vitro dissolution properties. Administration of slow-release tablets every 8 hr gave about the same mean plasma level at steady state as ordinary tablets given every 4 hr, and the availability was the same from both preparations. The occasional high plasma concentration peaks after ordinary tablets were not observed after the slow-release tablets. Renal clearance was about 500 ml/min, indicating an active secretion in the tubules.

Acetylation

The influence of food on side effects and absorption of lithium.

In a cross-over study, 24 mmol of lithium sulphate was given as a single dose in slow release tablets to 30 healthy volunteers fasting and after a standardised meal. Comparisons were also made with lithium citrate in slow release tablets and placebo. Postprandial administration of lithium gave practically no side effects, while lithium on an empty stomach gave diarrhoea in about 20% of the subjects. The absorption was measured by determination of the amount of lithium excreted in the urine in a group of ten subjects. Lithium was completely absorbed when given after food, but when given on an empty stomach the absorption was lower in some subjects, apparently due to rapid gastrointestinal passage in connection with diarrhoea. Lithium should therefore preferably be administered after meals.

Clinical Trials as Topic