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Biomedical subjects

T Sundqvist

Publications and source records attributed to T Sundqvist.

81 records · Page 5Linked to original sources

Altered intestinal permeability to low-molecular-weight polyethyleneglycols (PEG 400) in patients with Crohn's disease.

The passive intestinal permeability to different-sized low-molecular weight polyethyleneglycols (PEG 400) was studied in 24 patients with Crohn's disease, which were compared to 24 healthy persons. The recovery in 6-hour urine after oral intake was significantly lower (p less than 0.0005-0.005) in the subjects with Crohn's disease for molecules ranging between 282 and 546 in molecular weight. Mathematical modelling of the filtering properties demonstrated a lower filtering efficiency of the larger polyethyleneglycols in the patients than in the healthy individuals. The coefficient of variation for the different polymers was larger in the group of Crohn's disease patients, indicating greater heterogeneity in the intestinal filtering efficiency. In two patients the intestinal uptake of the probe molecules was increased 6 weeks after resectional surgery compared to the uptake before operation.

Adolescent↗

Modulation of polymorphonuclear leukocyte chemiluminescent response to the chemoattractant f-Met-Leu-Phe.

Upon the interaction between polymorphonuclear leukocytes (PMNL) and soluble or particulate matter, the cells become metabolically activated and produce chemiluminescence. To respond with chemiluminescence to the chemotactic peptide formyl-methionyl-leucyl-phenylalanine (f-Met-Leu-Phe), the PMNL required conditioning of the cells at 22 degrees C or higher temperature prior to stimulus addition. This was not required when phorbolmyristate acetate or opsonized yeast particles were used as stimulus. When cell samples were obtained from PMNL suspensions during 240 min from preparation, the chemiluminescence signal triggered by f-Met-Leu-Phe progressively increased. Scatchard plot analysis of the chemiluminescence data indicated that storage of the cells resulted in modulation of both the number of functional receptors and the affinity for the receptor. The importance of receptor function control in the inflammatory process is discussed.

Chemotactic Factors↗

Influence of fasting on intestinal permeability and disease activity in patients with rheumatoid arthritis.

We have investigated the influence of fasting and lactovegetarian diet on intestinal and non-intestinal permeability in 5 patients with rheumatoid arthritis. We used low-molecular weight polyethyleneglycols (PEG 400) as probe molecules and a deterministic mathematical model to assess the permeability characteristics. Both intestinal and non-intestinal permeability decreased after fasting, but increased again during a subsequent lactovegetarian diet regime. Concomitantly it appeared that disease activity, as shown by a clinical six-joint score, first decreased and then increased again. The results indicate that, unlike lactovegetarian diet, fasting may ameliorate the disease activity and reduce both the intestinal and the non-intestinal permeability in rheumatoid arthritis.

Arthritis, Rheumatoid↗

Computer-aided counting with the Coulter Counter of low numbers of spermatozoa in human semen.

The concentration of spermatozoa in human semen has been assessed by counting in the microscope with a hemocytometer and by counting with the Coulter Counter ZF. The Coulter Counter was supplied with a 100-channel pulseheight analyzer, Channelyzer C-1000, and a tape-punch for further handling of data in a desk-computer. It was found that the number of spermatozoa (less than 10(6) per ml) was over-estimated with the Coulter Counter. By subtraction of the non-spermatozoan background with the aid of mathematical curve-fitting procedures, these values could be corrected. To allow such an adequate analysis without the use of pulse-height analyzer and computer, the background corrections were simulated for the relative number of counts obtained at specified setting of the threshold levels (T) and other variables on the Coulter Counter ZF.

Computers↗

Passage of molecules through the wall of the gastrointestinal tract. Increased passive permeability in rat ileum after exposure to lysolecithin.

The interaction between lysolecithin and mucosal cells in the distal ileum has been studied. Using a rat experimental model, we determined the intestinal permeability to fluorescent dextran 3000 after exposure to different amounts of lysolecithin. At pH 7.3, lysolecithin, 10 mg/ml, significantly enhanced the transmural passage, and at pH 3.5, even 1 mg/ml markedly increased the permeability. However, when lysolecithin was incubated with homogenized mucosal cells, a rapid disappearance of the compound occurred; this was accompanied by formation of free fatty acids and minor formation of lecithin. It appears, therefore, that high concentrations of lysolecithin can impair the intestinal barrier function in the distal part of ileum but that the mucosal cells are well equipped with activities for the rapid removal of such high concentrations. This could be physiologically significant, since the mucosal cells could otherwise be faced with large amounts of lysolecithin that might facilitate the absorption of potentially antigenic and toxic compounds.

Animals↗

Passage of molecules through the wall of the gastrointestinal tract. II. Application of low-molecular weight polyethyleneglycol and a deterministic mathematical model for determining intestinal permeability in man.

The intestinal permeability to low molecular weight polyethyleneglycol (PEG) has been evaluated by means of a simple mathematical model and computer-aided curve-fitting procedures. Macrogolum 400, a mixture of 11 PEGs with molecular weights ranging from 194 to 634 daltons, was taken together with a liquid meal and a six-hour portion of urine collected. The different PEGs were then extracted from the urine, separated from each other by gas-liquid chromatography, and the relative peak area of each individual PEG determined. The distribution of different PEGs in the urine was then compared with the original PEG-distribution in three different ways: (1) by comparing the median values of the molecular weights, (2) by comparing the mean and standard deviation after curve fitting to the normal distribution, and (3) by curve fitting to mathematical filter functions demonstrating molecular exclusion due to size. It thus appeared that molecules were excluded both in the high and in the low molecular weight range, possibly by a combined effect of the intestinal permeability barrier and an escape to other compartments than the urine. However, relatively more of the larger PEGs passed from the intestine to the urine in a patient with Crohn's disease than in an apparently healthy individual.

Adult↗

Characteristics of individual polymorphonuclear leucocyte motility obtained with a new opto-electronic method.

An opto-electronic device has been used for a quantitative assessment of the motility of individual polymorphonuclear leucocytes (PMNL) adhering to a glass cover slip. One of the oculars in a phase contrast microscope is provided with a mini-array of 32 x 32 light-sensitive elements. These are connected to an electronic unit, capable of recording the number of light-intensity changes on each element and of visualizing the path of a cell on an oscilloscope screen, as a pattern of dots. The results clearly show that individual PMNL respond differently to environmental conditions; for instance, (i) raising the temperature increased the motility of cells to a maximum at around 39 degrees C and lowering the temperature from 42 degrees C restored their peak motility, (ii) protein was required at attachment depending on the temperature at attachment, (iii) endotoxin-activated normal human serum affected more drastically cells with a low initial motility and cytochalasin B more adversely influenced cells with a high initial motility, (iv) phagocytosis of yeast cells reduced the percentage of motile cells, which was more pronounced if the PMNL were washed before the motility measurement. The average motility of the PMNL was also diminished, although individual PMNL retained normal activity after ingestion of one or more yeast cells.

Animals↗

Characteristics of the phagocytic process assessed by Coulter Counter.

The phagocytosis in suspensions of heat-killed yeast cells, Saccharomyces cerevisiae, by human polymorphonuclear leucocytes was studied in vitro by means of an electronic particle counter, the Coulter Counter, and a 100-channel pulse-height analyzer, the Channelyzer. The two cell populations were separated from each other electronically by the Channelyzer. Phagocytosis was recorded as disappearence of yeast cells. Concomitantly, aggregation and swelling of the PMN-cells were observed, which increased with the concentration of the prey. The process could be inhibited by cytochalasin B and iodoacetamide. With the latter inhibitor, the analysis of the kinetics showed that ingestion, but not adhesion, was affected. The ingestion of yeast cells was augmented on increase of the initial ratio between the number of yeast and PMN cells to around 5:1, but was then reduced on further increase. A ratio of 2:1 and a reaction time of 30 min seemed suitable for studying the phagocytic process. First-order kinetics were obeyed under these circumstances.

Blood Cell Count↗

The effects of N-ethylmaleimide on extracellularly and intracellularly generated chemiluminescence in neutrophils indicate that the rate of deactivation of NADPH-oxidase is higher when the oxidase system is localized on the plasma membrane than when it is localized on the phagosomal membrane.

Sustained generation of reactive oxygen metabolites following respiratory burst activation in neutrophils is a result of continued replenishment of a pool of active NADPH-oxidase. The sulphydryl-modifying reagent N-ethylmaleimide (NEM) has been shown to be without effect on the turnover of activated NADPH-oxidase but to inhibit the replenishment of active oxidase molecules (Akard et al., 1988). NEM was thus used to determine the rate of deactivation of extracellularly and intracellularly generated chemiluminescence in human neutrophils. We have shown that deactivation is more rapid when activation leads to a release of oxygen metabolites (extracellular chemiluminescence) than when the metabolites are generated intracellularly. The results indicate that the rate of deactivation of NADPH-oxidase is higher when the oxidase system is localized on the plasma membrane than when it is localized on the phagosomal membrane.

Adult↗