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Biomedical subjects

C Nyström

Publications and source records attributed to C Nyström.

At least 19 recordsLinked to original sources
PubMed1992

Epithelial transport of drugs in cell culture. VII: Effects of pharmaceutical surfactant excipients and bile acids on transepithelial permeability in monolayers of human intestinal epithelial (Caco-2) cells.

The effects of anionic (sodium dodecyl sulfate and sodium dioctyl sufosuccinate) and nonionic (polysorbate 80 and polyoxyl 40 hydrogenated castor oil) synthetic surfactants and bile acids (sodium taurocholate, sodium taurodeoxycholate, and sodium taurodihydrofusidate) on epithelial integrity were studied in monolayers of human intestinal epithelial (Caco-2) cells grown on microporous polycarbonate filters. The effects of the surfactants on intracellular enzyme activity, cell monolayer permeability, and morphology were studied. The effects on permeability were studied by two methods: measurements of transport of marker molecules (mannitol and polyethylene glycol) and measurements of transepithelial electrical resistance. All surfactants demonstrated concentration-dependent effects on intracellular enzyme activities, permeability, and morphology. The effects of the anionic surfactants were more pronounced than those of the nonionic surfactants. The effects on transepithelial electrical resistance correlated with intracellular dehydrogenase activity. Fluxes of marker molecules were the most sensitive measure of epithelial integrity. The results indicate that the hydrophilic marker molecules permeate the epithelial monolayers through different pathways at different concentrations of the surfactants. The effects of the surfactants were reversible at intermediate concentrations, even though the morphology of the monolayers had changed. The results agree with published data obtained with experimental animals and indicate that Caco-2 cells can be used to study the concentration-dependent effects of surfactants and other pharmaceutical additives on intestinal epithelial permeability.

Bile Acids and Salts↗
PubMed1988

Relationships between EEG and biochemical parameters in major depressive disorder.

Twenty-five patients with major depressive disorder according to RDC were examined with computerized quantitative EEG before antidepressive treatment. Normal EEGs were found in 20 patients and slight abnormality in five cases. Relationships between various EEG variables and pretreatment accumulation rate of 14C-5-HT and 3H-NA in rat synaptosomes, incubated in patients' plasma, and 5-HT in whole blood were studied. Age and current treatment with benzodiazepines were taken into account. There was an inverse relationship between alpha-1 amplitude in all derivations and beta-2 amplitude in the parieto-occipital derivation on one hand and pretreatment 14C-5-HT synaptosomal accumulation rate on the other. This result indicates that low 14C-5-HT synaptosomal accumulation rate is related to increased EEG alertness. This EEG pattern is suggested to be associated with a serotonergic subgroup of depression. The relationships between the other biochemical variables and the EEG patterns did not show any consistent pattern.

Adult↗
PubMed1987

Comparison between a serotonin and a noradrenaline reuptake blocker in the treatment of depressed outpatients. A cross-over study.

Seventy-five outpatients with major depressive disorder (RDC) were randomly referred to treatment with a dominant serotonin (5-HT) reuptake blocker (zimeldine, 100 mg, b.i.d. n = 40) or a dominant noradrenaline (NA) reuptake blocker (maprotiline, 75 mg, b.i.d. n = 35). Seven patients on each drug were non-responders after up to 4 weeks of treatment and were after a washout week crossed over to the other drug for up to another 8 weeks of treatment. There was a significant and similar improvement after 4 weeks of treatment with the second drug. After up to 8 weeks of treatment all patients but one in each group were much improved with the second drug. The existence of two biochemical subgroups of depression is discussed.

Adult↗
PubMed1986

Comparison between a serotonin and a noradrenaline reuptake blocker in the treatment of depressed outpatients. Biochemical aspects.

Seventy-five outpatients with major depressive disorder (RDC) were randomly referred to treatment with a dominant 5-HT reuptake blocker (zimeldine, 100 mg b.i.d.) or a dominant NA reuptake blocker (maprotiline 75 mg b.i.d.). Pretreatment biochemical, pharmacodynamic and pharmacokinetic variables were studied and related to the treatment outcome with the two drugs. Female responders to the dominant 5-HT reuptake blocker were characterized by low pretreatment accumulation of 14C-5-HT in rat synaptosomes, when incubated in patient plasma. Among zimeldine responders there was a relationship between antidepressive effect and steady-state concentrations of zimeldine and norzimeldine. These findings support the hypothesis of a subgroup of depression characterized by serotonin disturbance.

Animals↗
PubMed1986

The use of ordered mixtures for improving the dissolution rate of low solubility compounds.

The dissolution rate of micronized griseofulvin has been investigated, both for the agglomerated raw material and the material formulated as an ordered mixture, by means of the USP XX paddle method. During the experiments, which were performed at sink condition and constant temperature, the effects of adding a surfactant and of agitation were tested. The ordered mixture with sodium chloride gave a fast dissolution rate, practically independent of the test parameters. Micronized griseofulvin alone gave dissolution profiles that were improved by adding polysorbate 80 and by increased agitation, but the dissolution rates obtained were much lower than those for the ordered mixture. It was concluded that the rate limiting step in the dissolution of griseofulvin as the raw material is the penetration of the dissolution medium into the agglomerates. With an ordered mixture, these agglomerates were deaggregated during the mixing process, producing a system in which the entire external surface area of the primary particles was exposed to the dissolution medium. This conclusion was supported by calculation of the contact surface areas taking part in the dissolution process for the systems tested. The procedure developed in this study could be applied to preformulation work where a cohesive, low solubility drug of hydrophobic nature is to be formulated.

Griseofulvin↗
PubMed1986

Coulter Counter measurements of solubility and dissolution rate of sparingly soluble compounds using micellar solutions.

A Coulter Counter, Model TAII, was used to determine both solubility and surface specific dissolution rate of two sparingly soluble materials suspended in micellar solutions. The equilibrium solubility increased linearly with surfactant concentration, thereby making it possible by extrapolation to characterize materials with an aqueous solubility down to 1 ppm or less. At high concentrations (greater than 0.1% w/v) the effect of surfactant concentration on the surface specific dissolution rate was less than that predicted from the increased bulk solubility.

Felodipine↗
PubMed1985

Double-blind comparison between a serotonin and a noradrenaline reuptake blocker in the treatment of depressed outpatients. Clinical aspects.

Seventy-five outpatients with major depressive disorder (RDC) were randomly referred to treatment with a dominant serotonin (5-HT) uptake inhibiting drug (zimeldine, 100 mg b.i.d.) or a dominant noradrenaline (NA) uptake inhibiting drug, (maprotiline, 75 mg b.i.d.). The total antidepressive effect was similar in the two groups for up to 4 weeks of treatment. Both drugs gave an effect on the depressive syndrome as a whole, with no preference for mood, anxiety, retardation or vital symptoms. Good response to the NA drug correlated to few prior episodes and few years since first episode, whereas the 5-HT drug had its best effect when there were several previous episodes.

Adult↗
PubMed1985

Dissolution rate measurements of sparingly soluble compounds with the Coulter Counter model TAII.

A Coulter Counter, Model TAII was used to determine both solubility and dissolution rate from suspensions of griseofulvin and hydrocortisone acetate, where the initial particle size and shape had been characterized. The method assesses the weights and surface areas of particles remaining undissolved as a function of time. A comparison with a conventional method, assessing dissolved quantities of materials, showed that solubility data of the same order of magnitude can be obtained. The TAII data fitted a previously established equation that linearly relates log solubility and log of the intrinsic dissolution rate and indicated that the dissolution process was not diffusion controlled. The TAII method described is a rapid and convenient means of estimating the solubility and dissolution rate where no adequate technique for analysing the dissolved fraction exists.

Chromatography, High Pressure Liquid↗
PubMed1978

Bile salt malabsorption in the radiation syndrome.

The fraction of faecal activity (FBS) excreted after intravenous administration of 14C-labelled cholic acid was measured in 20 patients with gastrointestinal symptoms (diarrhoea, abdominal pains, malabsorption and rectal haemorrhage) after pelvic irradiation. An FBS excretion of 52 +/- 16 per cent (mean +/- SD) was found in 13 patients with diarrhoea and 18 +/- 12 per cent in 7 patients without diarrhoea. In normals the excretion is not above 18 per cent. Bile salt malabsorption appears to be an important factor in the pathogenesis of diarrhoea in these patients.

Adult↗
PubMed1977

The size and shape of human and bovine antithrombin III.

Human and bovine antithrombin, purified by affinity chromatography on heparin-agarose, have been characterized with regard to chemical composition, size, shape and conformation. Both preparations were found to contain several active components of identical or similar size but different electrical charge. Amino acids and carbohydrate analyses revealed striking similarities between human and bovine antithrombin, while immunological analyses failed to demonstrate any cross-reactivity. The molecular weights were determined by sedimentation equilibrium to be 58 000 for human and 56 000 for bovine antithrombin. The small molecular weight difference suggested by these values was verified by several empirical methods of molecular weight estimation. Hydrodynamic measurements indicated that the two proteins have similar molecular shapes, both of which are slightly more extended that that of typical globular proteins. The internal folding of the two polypeptide chains is also similar, as evidenced by the identity of the far-ultraviolet circular dichroism spectra. Specifically, these analyses suggested a low alpha-helix content of both proteins. In conclusion, the marked structural similarity of human and bovine antithrombin indicates that the two proteins may also exhibit extensive functional similarities in the binding of heparin and the inhibition of various coagulation factors.

Amino Acids↗