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Biomedical subjects

T Sundqvist

Publications and source records attributed to T Sundqvist.

At least 55 records · Page 3Linked to original sources
PubMed1993

The cGMP modulator, LY83583 alters oxygen metabolites differently in cultured endothelial cells and isolated neutrophilic granulocytes.

The present study was designed to assess the effect of LY83583 on H2O2/O2- production from endothelial cells and neutrophils, as determined by chemiluminiscence generation in vitro. We found that LY83583 increased H2O2/O2-production from endothelial cells, but inhibited the H2O2/O2- production from phorbol myristate acetate-stimulated neutrophils. Furthermore, LY83583 consumed NADPH under certain conditions. Since neutrophils generate superoxide anion radicals via an NADPH-oxidase, we suggest that the reduction of chemiluminiscence, seen after addition of LY83583 to phorbol myristate acetate-stimulated neutrophils, is due to increased consumption of NADPH. In endothelial cells, NADPH is required as a co-factor in the generation of nitric oxide, which may interact with superoxide anion. A consumption in NAPDH would therefore be expected to decrease the production of nitric oxide and increase H2O2/O2-generation. The consumption of NADPH in endothelial cells could also cause reduced scavenger functions of the glutathion system, resulting in a further increase in H2O2 release.

Aminoquinolines↗
PubMed1993

Hydrogen peroxide stimulates endocytosis in cultured bovine aortic endothelial cells.

Fluid-phase uptake of macromolecules by cultured bovine aortic endothelial cells was measured using FITC-dextran (70,000 Da). Low doses of hydrogen peroxide added extracellularly stimulated the uptake of macromolecules by the endothelial cells. There was no general increase in the passive permeation or the transport across the cell layer. Moreover, when endothelial cells were stimulated with phorbol myristate acetate (PMA), macromolecules uptake was also enhanced. The PMA effect was blocked with superoxide dismutase (SOD) and catalase, suggesting a pivotal role of oxygen metabolites in fluid phase uptake of macromolecules by endothelial cells.

Animals↗
PubMed1992

Reduced intestinal permeability measured by differently sized polyethylene glycols in acute uremic rats.

The effect of experimental acute renal failure on the intestinal permeability measured by differently sized polyethylene glycols (PEG) was studied in rats. The permeability was assessed by analysing the 24-hour urinary recovery of PEG molecules (size 326-1,162 D). Acute renal failure was induced by clamping the left renal artery and right-sided nephrectomy. The overall urinary recovery of PEG was decreased in the uremic rats. However, the relative recovery of larger molecules (range 590-1,162 D) was further reduced in the uremic rats. The results which are compared with a computer simulation by a multicompartment model, suggest that the intestinal permeability especially towards larger PEG is decreased in acute uremic rats.

Acute Kidney Injury↗
PubMed1991

Bovine aortic endothelial cells release hydrogen peroxide.

Endothelial cells grown on microcarriers are able to release H2O2 to the extracellular environment without any added stimulus. The extracellularly released H2O2 can be detected by luminol-amplified chemiluminescence (CL) if horseradish peroxidase is added. The CL response can be reduced by catalase and blocked by superoxide dismutase, indicating that O2- could be a precursor for H2O2. The CL kinetics, i.e., a long lag time followed by a rapid shift to a new level, indicate activation of an O2(-)-producing enzyme. The cells are also able to protect themselves from H2O2 stimulation by both catalase and the glutatione system. Bradykinin stimulates the H2O2 release, but if the effect is directly stimulatory or if it acts by reduction of the protective system is at present unclear. The extracellularly released H2O2 could be a cause of injury to the endothelial cells or to the subendothelial matrix.

Animals↗
PubMed1991

Intestinal permeability in patients with yersinia triggered reactive arthritis.

The passive intestinal permeability of patients with yersinia triggered reactive arthritis was studied using different sized polyethylene glycols (PEGs) contained in a mixture of PEG 400 and PEG 1000. The investigation was carried out at least one year after the onset of yersinia infection, and patients had neither acute gastrointestinal nor joint symptoms. The control groups included patients with uncomplicated yersiniosis as well as healthy subjects who were either HLA-B27 positive or negative. An altered intestinal barrier function to PEG molecules was detected in patients with a history of yersinia infection compared with healthy controls. No significant differences in the permeability were found between patients with or without reactive arthritis, nor was there any association of increased permeability with HLA-B27. The passive permeability of the intestinal mucosa to the larger molecules was increased for an unexpectedly long time after the acute yersinia infection, probably contributing to the perpetuation of joint symptoms in subjects susceptible to a chronic joint disease.

Adult↗
PubMed1991

Impaired intestinal barrier function measured by differently sized polyethylene glycols in patients with chronic renal failure.

The intestinal mucosa plays a fundamental role as the site for absorption of nutrients, and as an important barrier from potentially harmful agents in the intestinal lumen. Little is known of the permeability properties of the intestinal mucosa in uraemic patients. The intestinal permeability to differently sized polyethylene glycols (PEGs; range 326-1254 daltons) was studied in nine patients with chronic renal failure (24 hour endogeneous creatinine clearance 5-24 ml/minute). The maximum 24 hour urinary recovery of PEGs was decreased in the uraemic patients but relatively more of the larger than the smaller PEGs were found in these patients. The results suggest a reduced urinary recovery of PEGs caused by renal dysfunction but also a relatively increased intestinal permeability to larger PEGs in the uraemic patients.

Adult↗
PubMed1990

Increased intestinal permeability to differently sized polyethylene glycols in uremic rats: effects of low- and high-protein diets.

Intestinal mucosa forms an important barrier towards harmful agents in the intestinal lumen, besides being the site for absorption of nutrients. Little is known about the intestinal permeability properties in chronic uremia. The permeability toward differently sized polyethylene glycols (PEGs; range 326-1,162 Da) was studied in uremic groups compared to the control groups. The urinary recovery was also recovery of PEGs was increased in the uremic groups compared to the control groups. The urinary recovery was also increased in the groups on the high-protein diet compared to the corresponding group on the low-protein diet. This study suggests an increased permeability of PEG molecules in the range of 546-1,162 Da in uremic rats and a decreased intestinal permeability after a low-protein diet in both a uremic and nonuremic state. Thus, in chronic renal failure the intestinal barrier is impaired but returns towards normal with low-protein diets.

Animals↗
PubMed1990

Urinary excretion of differently sized polyethylene glycols after intravenous administration in uremic and control rats: effects of low- and high-protein diets.

The intestine constitutes a barrier towards potentially harmful agents in the intestinal lumen. Different-sized polyethylene glycols (PEGs; range 326-1,1162 Da) have been used to study the intestinal permeability properties in 5/6-nephrectomized rats on either a high- (22%) or low-protein (8%) diet. PEGs were administered intravenously, and the urinary recovery was measured. The 24-hour urinary recovery of PEGs was significantly reduced in the uremic groups. The ratios between different sizes of PEGs, indicating a size-selective escape of molecules from blood, were decreased in the uremic groups. The urinary recovery was in general increased in the control group on the high-protein diet compared to the control group on the low-protein diet. The results provide evidence for an increased permeability of larger PEGs (range 634-1,162 Da) in uremic rats and that the protein content of the diet might affect the permeability properties.

Animals↗
PubMed1989

Intestinal permeability to inert sugars and different-sized polyethyleneglycols in children with celiac disease.

Intestinal permeability was measured in a total of 42 children, 29 of whom had celiac disease. The celiac children were studied at presentation, during gluten-free diet, and/or at gluten challenge. The permeability was assessed by oral lactulose/L-rhamnose in all 42 children and also by different-sized polyethylene glycols (PEG) in 36 children. Results were compared with the findings of small intestinal biopsy. The mean of the permeability tests in children with enteropathy was significantly abnormal compared with the result in children with a normal mucosal morphology. The lactulose/L-rhamnose test and the PEG test gave equivalent results in the same child. In the celiac children abnormal permeability properties at presentation normalized during gluten-free diet and reappeared during gluten challenge. It is concluded that measurement of intestinal permeability may be a valuable tool in monitoring children with celiac disease, preferably when serial measurements are available in the same child.

Adolescent↗
PubMed1989

Intestinal permeability assessed with polyethylene glycols in children with diarrhea due to rotavirus and common bacterial pathogens in a developing community.

Intestinal permeability was assessed with different-sized polyethylene glycols (PEG 400 and PEG 1,000) in small children with acute diarrhea. All children with acute diarrhea absorbed and excreted less PEG of all molecular sizes into the urine when compared with healthy control children (p less than 0.001). Children with acute rotavirus infection excreted significantly less PEG of all sizes than children with Shigella, Salmonella, and enteropathogenic Escherichia coli (EPEC) infection (p less than 0.001-0.01), suggesting a more severe mucosal lesion caused by rotavirus. In patients with severe malnutrition there was also a significant decrease in absorption of PEGs observed. In addition, malnourished patients with rotavirus diarrhea showed a pronounced decrease of PEGs in comparison with well-nourished patients. The ratio between the recovery of a large PEG molecule, 1,074 Da, and a small molecule, 370 Da, was utilized to assess the absorption of large molecules in relation to that of smaller ones. On applying this ratio, it was noted that the intestine in children with Shigella and EPEC infection was relatively more permeable to larger molecules than in healthy controls, while in rotavirus and Salmonella infection it was less permeable to larger molecules. In this study significant differences in the permeability characteristics were observed, suggesting etiology-specific effects on the mucosal barrier.

Child, Preschool↗
PubMed1989

Intestinal permeability assessed with different-sized polyethylene glycols in children undergoing small-intestinal biopsy for suspected celiac disease.

The gastrointestinal permeability was assessed by means of an oral load of a mixture of different-sized polyethylene glycols (PEG 400 and PEG 1000) in 76 children undergoing small-intestinal biopsy because of suspected celiac disease. Children with a mucosal abnormality suggestive of celiac disease had a lower urinary recovery of larger PEG molecules. They also displayed an altered permeability barrier, as evidenced by a lower ratio of recovery between large (1074 Da) and small (370 Da) PEG molecules. Gluten elimination and gluten challenge caused a significant change in PEG recoveries in children undergoing repeated PEG tests. Repeated assessments of intestinal permeability by means of different-sized PEGs after gluten withdrawal and challenge could complement or indicate suitable time for performing small-intestinal biopsy in children with gluten intolerance.

Adolescent↗
PubMed1988

Lateral diffusion of the secretory component (SC) in the basolateral membrane of the human colon carcinoma cell line HT29 assessed with fluorescence recovery after photobleaching.

The lateral diffusion of the secretory component (SC), acting as a receptor for dimeric IgA in the basolateral side of intestinal epithelial cells, was studied in the human colonic carcinoma cell line HT29. The HT29 cells were grown in Dulbecco's modified Eagle's medium in which galactose had been substituted for glucose to promote development of small intestine-like cells, with a distinct separation of the basolateral side from the apical surface. The SC was stained with rhodamine-labeled polyclonal anti-human SC rabbit antibodies (Ig) or Fab fragments, and the lateral mobility was assessed with the fluorescence recovery after photobleaching technique. The average lateral diffusion was consistent with a diffusion constant of 7.7 +/- 2.0 (mean value +/- SD; n = 29) and 7.1 +/- 2.3 (n = 30) x 10(-10) cm2s-1 for Ig-and Fab-labeled receptors, respectively, which is slower than lipid diffusion but is similar to that found for other membrane receptors. The corresponding values for the fraction of mobile receptors were 66 +/- 13% and 71 +/- 12%, respectively. Cells were labeled from the top of the culture plate, and cells adjacent to a mechanically made rift or a natural opening in the cell monolayer were labeled more strongly, confirming the microscope-based impression that the basolateral surface primarily harboured the SC receptor.

Colonic Neoplasms↗
PubMed1988

Characterization of size-dependent exchange of PEG molecules between the blood and extravascular space in the pig.

Different sized polyethylene glycols (PEGs) have been used as probe molecules in studies of size-dependent permeation through the intestinal wall and the glomerular membranes. We have curve-fitted a three-compartment model to the urinary recovery data following intravenous injection of different sized PEG molecules in the pig. The rate constants to and from the extravascular space demonstrate a strong size-dependent selectivity for PEG molecules less than 502 Da, but the rate constants to the urine are almost the same for all PEG molecules. This is discussed in relation to the selectivity in the glomerular filtration, distribution volume, and the use of PEG molecules as tracers in the permeability studies.

Animals↗
PubMed1988

Elimination kinetics of circulating antigens and immune complexes. II. Hepatic and extrahepatic elimination of chemically modified albumin preparations in relation to their non-specific physicochemical properties.

Formaldehyde-treated human serum albumin (fHSA) was analysed and compared with dinitrophenylated human serum albumin (DNP35HSA) with respect to net charge, hydrophobicity, and state of aggregation. The blood clearance and tissue distribution of intravenously injected fHSA was studied in mice. Similarly to DNP-HSA, fHSA was rapidly cleared from the blood stream owing to hepatic uptake and to extrahepatic deposition. We found no evidence supporting that fHSA was eliminated from the blood by hydrophobic interaction with cell or tissue surfaces. The blood clearance rate and the hepatic uptake of fHSA was not influenced by the presence of formylated peptides, indicating that receptors for formylated peptides were not involved in the handling of circulating fHSA.

Animals↗
PubMed1988

Elimination kinetics of circulating antigens and immune complexes. I. A simple multicompartment model for the analysis of blood elimination of intravenously injected antigens and immune complexes.

A multi-compartment model designed to analyse the blood elimination kinetics of intravenously injected radiolabelled antigens in experimental animals is presented. The model was fitted to experimental data on blood radioactivity levels at different times following intravenous injection of radiolabelled antigen. Numerical values were obtained for tissue association, degradation, and urinary recovery of degradation products. The model may prove useful as a test for reticuloendothelial function.

Animals↗
PubMed1988

Elimination kinetics of circulating antigens and immune complexes. III. Elimination of intravenously injected model antigens and soluble IgG immune complexes in mice.

The blood elimination kinetics of model antigens, i.e. dinitrophenyl-conjugated human serum albumin (DNP-HSA) preparations, and soluble immune complexes (IgG-anti-DNP + DNP-HSA) were analysed by the aid of a multicompartment model, allowing estimation of tissue uptake and degradation of the immune complexes (ICs). The haematocrit values remained stable after intravenous injection of the ICs in mice. Despite this fact, the blood clearance kinetics were excellently described by three exponential functions. This indicates that the rapid initial elimination of the ICs from the blood was not the result of IC-induced capillary leakage, but rather of rapid initial binding of the complexes to different tissue structures. We also present results indicating that the elimination of circulating complexes/protein aggregates is governed less by their size than by other physical/chemical properties.

Animals↗
PubMed1987

Rapid lateral diffusion of lectin-labelled glycoconjugates in the human colonic adenocarcinoma cell line HT29. Comparison with the synthetic lipid analogue diI-C14.

The lateral diffusion of lectin-labelled glycoconjugates was studied in the human colon carcinoma cell line HT29 using fluorescence photobleaching techniques. HT29 cells were grown in either Dulbecco's modified Eagle's medium with glucose (25 mM; DMEM-Glu) or with galactose (25 mM; DMEM-Gal). Cell cultivation in the DMEM-Gal medium was assumed to promote a transformation of the cells to become small-intestinal-like with characteristic microvilli and associated enzymes. The diffusion of glycoconjugates labelled with fluoresceinated Triticum vulgaris agglutinin (Wheat germ agglutinin; WGA), Ricinus communis agglutinin-I (RCA-I), Concanavalia ensiformis agglutinin (ConA), Ulex europaeus agglutinin-I (UEA-I) and Arachis hypogaea agglutinin (PNA) was in all cases rapid, with a diffusion constant (D) ranging between 0.4 and 0.8 X 10(-8) cm2 s-1. As a comparison the diffusion of the fluorescent synthetic lipid analog diI-C14 was characterized by D = 0.8 - 1.0 X 10(-8) cm2 s-1. The diffusion of lectin-labelled surface components could not be related to the presence of microvilli on HT29 cells grown in DMEM-Gal, which ought to yield an apparently lower diffusion rate. The results indicate either that surface glycoconjugates in HT29 cells are dominated by glycolipid, or that the labelled glycoproteins are more or less free to diffuse in the plane of the membrane.

Adenocarcinoma↗