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S B Pedersen

Publications and source records attributed to S B Pedersen.

At least 73 records · Page 4Linked to original sources
PubMed1992

Characterization of nuclear corticosteroid receptors in rat adipocytes. Regional variations and modulatory effects of hormones.

The corticosteroid receptor was investigated in isolated rat adipocytes with a new technique which characterizes the corticosteroid receptors that can be activated and tightly bound to the nucleus. The binding reaction with [3H]triamcinolone was performed with intact isolated adipocytes and the radioactivity associated with nucleus was subsequently determined after cell lysis. Scatchard analysis revealed a homogeneous class of nuclear corticosteroid receptors in rat epididymal adipocytes with an apparent Kd of 4.93 +/- 1.5 nM and a Bmax of 21.8 +/- 6.6 fmol/10(6) cells corresponding to about 13,000 receptors per nucleus. The corticosteroid binding exhibited regional variations in isolated adipocytes. The highest receptor number was found in epididymal adipocytes (Bmax 25.8 +/- 3.9 fmol/10(6) cells) whereas there were significantly lower nuclear binding sites in perirenal adipocytes (16.5 +/- 5.5 fmol/10(6) cells) (P less than 0.05) and subcutaneous adipocytes (4.8 +/- 1.5 fmol/10(6) cells) (P less than 0.01). The apparent affinity in the three fat depots were similar with Kd values about 4 nM. The nuclear corticosteroid receptor in adipocytes was steroid specific, as neither unlabelled estradiol nor testosterone were able to displace the [3H]triamcinolone binding at concentrations up to 100 microM. However, unlabelled progesterone and promegestrone (R5020) were able to compete with triamcinolone-binding (by 50-80%). In order to investigate whether the nuclear corticosteroid binding in adipocytes were under influence of other hormones we examined the effects of lipolytic and antilipolytic compounds on the binding. Preincubation with isoproterenol and dibutryl-cAMP for 1 h was able to decrease the corticosteroid binding by 30-50%. However, the antilipolytic hormone insulin had no effect in preincubations performed for up to 2 h. In conclusion, high affinity nuclear corticosteroid receptors were found in rat adipocytes. These receptors exhibited regional variations and were modulated by lipolytic hormones.

Adipose Tissue↗
PubMed1992

Effects of in vivo estrogen treatment on adipose tissue metabolism and nuclear estrogen receptor binding in isolated rat adipocytes.

We have previously demonstrated the existence of nuclear estrogen receptors in isolated adipocytes (Pedersen et al. (1991) Biochim. Biophys. Acta 1093, 80-86). In the present study we have investigated the regulatory properties of these nuclear estrogen receptors, in addition to the metabolic effects of estrogen on adipose tissue metabolism. Estrogen treatment (20 micrograms 17 beta-estradiol in NaCl for 7 days) decreased lipoprotein lipase activity (LPL) in the adipose tissue by 62% (p less than 0.05), decreased adipocyte size by 27% (p less than 0.01) and diminished the normal postovariectomy weight gain. Furthermore, estrogen treatment increased the nuclear estrogen receptor binding in adipocytes; in addition, there was a tendency for increased cytosolic estrogen receptor content as well. Time course studies revealed that already 6 h after a single estrogen injection the Bmax increased from 3.82 +/- 0.3 fmol/10(6) cells to 9.8 +/- 3.6 fmol/10(6) cells (p less than 0.1) and 24 h after a single injection the Bmax was maximally increased to 12.7 +/- 5.5 fmol/10(6) cells (p less than 0.05). The Kd was similar at all time points (about 3-5 nM). Furthermore, the specific insulin receptor binding was increased in adipocytes from estrogen treated rats. The specific insulin binding was maximally increased by 149 +/- 6% (p less than 0.001) after 4 days of daily estrogen injections. The increased binding seemed to be due to an increased number of insulin receptors on adipocytes from estrogen treated rats with no alteration of the ED50 value. In conclusion it was found that estrogen treatment has a positive feedback effect on its own nuclear receptor.(ABSTRACT TRUNCATED AT 250 WORDS)

Adipose Tissue↗
PubMed1992

Increased ornithine decarboxylase activity in kidneys undergoing hypertrophy in experimental diabetes.

Renal hypertrophy and hyperfiltration are early manifestations of human and experimental diabetes that may contribute to the late development of diabetic nephropathy. The biochemical events resulting in kidney growth in the diabetic state are completely unknown. Since growth of various tissues is accompanied by increased formation of polyamines, we studied whether polyamines were involved in the growth of the kidney observed in diabetic rats. This was done by measuring the activity of the rate-limiting enzyme in the polyamine pathway (ornithine decarboxylase; ODC) in kidneys from control, diabetic and insulin-treated diabetic animals. The ODC activity in the kidney was increased in the diabetic animals with a maximal rise 24 h after diabetes induction (6-fold, P less than 0.01); the activity thereafter declined. However, on day 14 the activity was still significantly elevated (2.5-fold, P less than 0.05). In insulin-treated diabetic animals the kidney ODC activity was only increased 3-fold (P less than 0.05) after 24 h, and for the rest of the study period the activity was about 1.8-fold higher than in control rats. After 14 days the kidneys from diabetic rats were significantly larger than kidneys from both control and insulin-treated diabetic rats, 1066 +/- 43 mg vs. 904 +/- 16 mg and 959 +/- 36 mg, respectively (P less than 0.01). For comparison, the ODC activity was also investigated in muscle. However, in muscle from diabetic animals the ODC activity declined steadily during the 14 days to 34% of control values (P less than 0.01), and insulin treatment completely normalized the ODC activity in muscle.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1991

Nuclear estradiol binding in rat adipocytes. Regional variations and regulatory influences of hormones.

The nuclear estrogen receptor was characterised in isolated rat adipocytes. The binding reaction with [3H]estradiol was performed with intact isolated rat adipocytes and the radioactivity associated with the nucleus was subsequently determined after cell lysis. The nuclear uptake of [3H]estrogen in rat adipocytes was temperature dependent and steroid specific. The steady-state binding was achieved after 30 min at 37 degrees C and was constant for several hours. Estradiol was found to bind to a homogeneous class of nuclear receptors in epididymal adipocytes with an apparent Kd of 3.1 +/- 0.76 nM and a Bmax of 7.98 +/- 1.11 fmol/10(6) cells corresponding to about 4800 receptors per nucleus. The estradiol binding exhibited regional variations in isolated adipocytes. In lean rats the highest receptor number was found in epididymal adipocytes, whereas there was a significantly lower number of nuclear binding sites in perirenal and subcutaneous adipocytes (P less than 0.05), unlike in older and more obese rats where the nuclear estradiol binding was greatest in adipocytes from the perirenal fat depot. Incubations with isoproterenol (10 microM) and dibutyryl-cAMP (2.5 mM) both reduced estradiol binding by 56% (P less than 0.005), while insulin (1 nM) enhanced the estradiol binding by 37% (P less than 0.01). In conclusion, a specific and high affinity nuclear estradiol receptor was demonstrated in rat adipocytes and regional differences in nuclear estradiol binding were detected. Furthermore, it was demonstrated that nuclear estradiol binding could be modulated by other agents known to affect adipocyte metabolism.

Adipose Tissue↗
PubMed1991

Phosphoinositide metabolism in adipocytes from hypothyroid rats.

The effect of hypothyroidism on insulin- and epinephrine-stimulated phosphoinositide metabolism was investigated in rat adipocytes. Insulin-mediated phosphoinositide synthesis was enhanced by hypothyroidism (14.5 +/- 1.5% above basal level, control vs. 22.5 +/- 2.0% above basel level, hypothyroid, P less than 0.05). However, insulin did not stimulate hydrolysis of phosphoinositides to inositol phosphates, neither in control nor in hypothyroid rats. The alpha 1-adrenoceptor agonist (e.g. epinephrine) significantly stimulated the incorporation of myo-[3H]inositol into phosphoinositides (P less than 0.01) and hydrolysis of phosphoinositides (P less than 0.01), but this stimulatory action was unaffected by the hypothyroid state. The results suggest that hypothyroidism has differentiated effects on the hormone-regulated phosphoinositide metabolism and that the presumptive G-protein coupled to the alpha 1-adrenoceptor seems to be unaffected by hypothyroidism.

Adipose Tissue↗
PubMed1991

Regional differences in triglyceride breakdown in human adipose tissue: effects of catecholamines, insulin, and prostaglandin E2.

Regional variation of adipose tissue triglyceride breakdown (lipolysis) has been suggested to play a role for the health consequences of some forms of obesity. Thus, in the present study we investigated the regulation of lipolysis in isolated adipocytes obtained from different fat depots in females. Intra-abdominal adipose tissue (omental) and subcutaneous abdominal adipose tissue were obtained from the same individuals undergoing abdominal surgery (n = 9); in addition, adipocytes from the subcutaneous gluteal region (n = 12) and from mammary adipose tissue (n = 5) were investigated. The lipolytic/antilipolytic properties of epinephrine (EPI), insulin, clonidine, and prostaglandin E2 (PGE2) were investigated. The most prominent observation was that EPI had none or only minor lipolytic effect in adipocytes from the subcutaneous regions, but significantly enhanced lipolysis by approximately 500% in omental adipocytes (P less than .001). In the presence of the alpha 2-adrenergic antagonist, yohimbine, EPI had similar stimulatory effects (fourfold to fivefold) in all fat depots. The antilipolytic compounds, insulin and clonidine, had greatly reduced antilipolytic properties in omental adipocytes as compared with subcutaneous adipocytes (P less than .01 and P less than .05, respectively). On the other hand, PGE2 had similar antilipolytic properties in adipocytes from the various depots. In conclusion, we found great regional variation in the regulation of lipolysis. Particularly, EPI was much more lipolytic in omental adipocytes than in subcutaneous adipocytes, mainly due to an enhanced functional alpha 2-receptor activity in subcutaneous adipocytes. These in vitro data suggest that free fatty acids (FFA) are more readily mobilized from omental adipose tissue than from subcutaneous adipose tissue.

Adenosine↗
PubMed1990

Relations between accommodation and vergence in darkness.

Prior studies reported that the resting postures of accommodation and vergence are uncoupled in darkness, calling into question whether accommodation-vergence synkinesis persists when both systems are deprived of stimulation. We tracked the postures of accommodation and vergence of 20 normal subjects for 15 min in darkness, using a Vernier optometer and dichoptic nonius lines. Consistent with previous reports, the mean resting postures of accommodation and vergence correlated weakly (r = 0.19); spontaneous fluctuations of accommodation and vergence in darkness also exhibited little correlation (median r = 0.15). However, resting vergence postures could be predicted (r = 0.65) from the clinically measured distance phoria and the resting posture of accommodation, when subjects' AC/A ratios were taken into account. We conclude that the relaxation of accommodation and vergence to separate resting postures in darkness is compatible with the persistence of synkinesis; independent noise in the two systems may reduce apparent coupling under open-loop conditions.

Accommodation, Ocular↗
PubMed1989

Characterization of antilipolytic action of polyamines in isolated rat adipocytes.

The interactions of polyamines with the lipolytic system were studied in isolated rat adipocytes. Spermine, spermidine and putrescine significantly inhibited adenosine deaminase-stimulated lipolysis. An antilipolytic effect of spermine was detectable at a concentration of 0.25 mM (P less than 0.05). At a concentration of 10 mM all three polyamines inhibited the stimulated lipolysis by 50-60% (P less than 0.001). In addition, spermine enhanced the antilipolytic sensitivity of insulin. Spermine (1 mM) decreased the half-maximal inhibitory concentration of insulin from 320 +/- 70 pM to 56 +/- 20 pM (P less than 0.01). The antilipolytic effects and the cyclic-AMP-lowering effects of the polyamines were almost completely prevented in the presence of different phosphodiesterase (PDE) inhibitors (3-isobutyl-1-methylxanthine and RO 20-1724) and, in addition, polyamines had no effect on lipolysis stimulated by dibutyryl cyclic AMP, indicating that polyamines may inhibit lipolysis by activating the PDE enzyme. This latter suggestion was confirmed by demonstrating that spermine (5 mM) significantly enhanced the low-Km PDE enzyme activity (P less than 0.01). Finally, the amounts of polyamines present in isolated adipocytes were measured, and the estimated cytoplasmic concentrations were 0.02 mM (putrescine), 0.86 mM (spermidine), and 1.0 mM (spermine). It is concluded that polyamines may possibly be involved in the physiological regulation of triacylglycerol mobilization in adipocytes.

1-Methyl-3-isobutylxanthine↗
PubMed1989

Polyamines in rat adipocytes: their localization and their effects on the insulin receptor binding.

Effects of polyamines on the insulin binding in isolated rat adipocytes were studied. In addition, the concentration of polyamines in adipose tissue was determined, and their localization revealed by fluorescence cytochemistry and immunocytochemistry. Spermine (0.1-10 mM) dose-dependently enhanced the insulin receptor binding; at a concentration of 5-10 mM spermine the insulin binding was enhanced by 100% above control values. Spermidine had a weaker effect than spermine whereas putrescine had no effect on insulin binding. Competition curves with unlabelled insulin indicated that spermine increased the insulin binding capacity without significantly affecting the binding affinity. Fluorescence and immunocytochemistry on adipose tissue localized the polyamines spermidine and/or spermine almost exclusively to the thin layer of adipocyte cytoplasm surrounding the lipid droplet. In addition, chemical analysis for polyamines in the adipocyte medium and in the cells indicated that a differential release of polyamines may have occurred from the cells. The possibility that polyamines may act as intracellular or intercellular (autocrine) regulators, modulating insulin binding, is discussed.

Adipose Tissue↗
PubMed1987

Antilipolytic effect of prostaglandin E2 in perifused rat adipocytes.

Previously, the antilipolytic effect of prostaglandin E2 (PGE2) has been investigated in conventional adipocyte incubations. To define the effect of PGE2 on lipolysis more clearly, isolated epididymal adipocytes were studied with the perifusion system. PGE2 inhibited isoproterenol (100 nM)- and theophylline (1 mM)-stimulated lipolysis in a concentration-dependent manner in both the perifusion system and conventional incubations. However, the half-maximally inhibitory concentration (ED50) of PGE2 on isoproterenol-induced lipolysis was about 0.4 nM in the perifusion system, whereas the ED50 was 8 nM in the static adipocyte incubations. The ED50 values of PGE2 on theophylline-induced lipolysis were 0.8 nM (perifusion) and 5 nM (incubation), respectively. Thus, the sensitivity of stimulated lipolysis to PGE2 was about 10 times higher in the perifusion system than in conventional adipocyte incubations. In addition, the maximal antilipolytic effect of PGE2 was greater in the perifusion system. At a concentration of 100 nM PGE2 inhibited theophylline-induced lipolysis by 82 +/- 5% in adipocyte incubations, whereas lipolysis was inhibited by 100 +/- 3.5% in the perifusion system (P less than 0.05). When lipolysis was stimulated by isoproterenol the maximal antilipolytic effect of PGE2 was an inhibition of 90 +/- 2.5% in the perifusion system and 55 +/- 5% in adipocyte incubations (P less than 0.05). Moreover, the maximal antilipolytic effect was obtained at a PGE2 concentration of 20 nM in the perifusion system, but at a concentration of 100 nM in static incubations. The release of immunoreactive PGE2 from adipocytes was measured by RIA. In the perifusion system no PGE2 could be detected in the effluent under basal conditions; however, during exposure to 100 nM isoproterenol a small amount of PGE2 was detected (3-4.5 pg/10(6) cells X min). Exogenous PGE2 was almost totally (90%) recovered in the effluent. In adipocyte incubations basal PGE2 production was 103 +/- 22 pg/10(6) cells X 60 min, whereas both isoproterenol and theophylline increased these amounts of PGE2 2-fold (P less than 0.01). It is concluded that exogenous PGE2 has pronounced antilipolytic properties at very low concentrations (subnanomolar) in perifused adipocytes. The reduced sensitivity and maximal responsiveness of PGE2 in static incubations may be related to accumulation of FFA and endogenous PGs, which may partially obscure the interaction of exogenous PGE2 with the adenylate cyclase complex.

Adipose Tissue↗
PubMed1986

Assay of tolfenamic acid and its metabolites by liquid chromatography on dynamically modified silica: application in pharmacokinetics.

An LC method able to separate all known metabolites of tolfenamic acid was developed. It was applied to characterize the metabolic profiles after single and multiple peroral doses of tolfenamic acid to volunteers. Up to 80% of the dose, mostly conjugated metabolites, could be recovered in the urine by this method. Two of the metabolites showed plasma half-lives of several days and peculiar conjugation properties.

Journal Article↗
PubMed1985

Pharmacokinetics of tolfenamic acid in patients with cirrhosis of the liver.

Six patients with alcoholic cirrhosis of the liver received 100 mg tolfenamic acid p.o. and i.v. The disposition of tolfenamic acid could be described by a two-compartment open body model, with a mean central compartment volume of 8.71, and a beta-phase volume of 25 l. The elimination rate constant ke averaged 1.13 h-1 and the half-life of the beta-phase was 1.73 h; the mean total plasma clearance was 159 ml/min. These pharmacokinetic parameters differed only slightly from those in two groups of healthy volunteers studied previously; ke was significantly reduced by about 30% in the patients but none of the other parameters differed significantly. There was good correlation between individual elimination rate constants or plasma clearances with the liver function tests, serum albumin and P-coagulation factors. Oral absorption was good and bioavailability of about 100% was shown by comparison of the areas under the plasma concentration - time curves after i.v. and p.o. administration. Metabolism was qualitatively and quantitatively very similar to previous observations in healthy volunteers. There seems no reason to reduce the dose of tolfenamic acid in patients with compensated alcoholic cirrhosis.

Adult↗
PubMed1981

Tolfenamic acid. Detection and structure of urinary metabolites.

N-(2-Methyl-3-chlorophenyl)anthranilic acid (tolfenamic acid) and its metabolites in serum and urine were analyzed by a reversed-phase ion-pair HPLC method. The major metabolites were N-(2-methyl-3-chloro-4-hydroxyphenyl)anthranilic acid, and one of the minor metabolites was N-(2-formyl-3-chlorophenyl)anthranilic acid, i.e., products resulting from hydroxylation in either the methyl group or the methylchlorophenyl group of tolfenamic acid, and further oxidation of the hydroxymethyl group to a formyl group.

Adult↗
PubMedDate not supplied

Regulation of plasminogen activitor inhibitor-1 in human adipose tissue: interaction between cytokines, cortisol and estrogen.

To investigate further the role of plasminogen activator inhibitor-1 (PAI-1) in human adipose tissue, the regulation of cytokines, cortisol (dexamethasone) as well as estrogen on PAI-1 were determined in human adipose tissue fragments. PAI-1 activity was increased in human adipose tissue fragments incubated for 48 h with interleukin-1beta (IL-1beta) (2.6-fold, p < 0.01) and tumor necrosis factor-alpha (2.3-fold, p < 0.01). Incubation with interleukin-6 revealed a non-significant decrease in PAI-1 activity. Parallel findings were obtained when studying the PAI-1 mRNA expression. Dexamethesone increased PAI-1 activity after incubation for 8 h (p < 0.05) and enhanced the stimulation of IL-1beta after 8 h incubation. However, after 24 and 48 h, dexamethasone significantly reduced the IL-1beta induced increase in PAI-1 activity by 24-52% (p < 0.05), accordingly, PAI-1 mRNA expression was reduced 60%. Finally, the induction of PAI-1 activity and PAI-1 mRNA expression by IL-1beta was attenuated by estrogen (17.8+/-4.9%, p < 0.05 and 20.9+/-5.8%, p < 0.05, respectively). These results indicate that multiple cytokines, estrogen and dexamethasone may be involved in the regulation of PAI-1 biosynthesis in human adipose tissue, and suggest that there are interactions between cytokines and these steroid hormones. The interplay between these hormones may be of importance for the levels of PAI-1 observed in obesity and associated states.

Adipose Tissue↗
PubMedDate not supplied

Interleukin-8 production in human adipose tissue. inhibitory effects of anti-diabetic compounds, the thiazolidinedione ciglitazone and the biguanide metformin.

Obesity and Type 2 diabetes are associated with an increased risk of developing cardiovascular disease. Reports have suggested that the chemokine, interleukin-8, may be involved in the development of diabetic macroangiopathy as well as in the pathogenesis of atherosclerosis. Two classes of drugs, the biguanides and the insulin-sensitizing thiazolidinediones seem to have additional beneficial effects on cardiovascular risk-factors besides their effects on glucose homeostasis. In this study, we investigated the effects of the thiazolidinedione, Ciglitazone, the peroxisome proliferator-activated receptor alpha-agonist 5,8,11,14-eicosatetraynoic acid (ETYA) and the biguanide, Metformin on interleukin-8 gene expression and production in human adipose tissue in vitro. Ciglitazone 10-100 M inhibited interleukin-8 release by 25-33% (p < 0.05) and mRNA expression by 33-60% (p < 0.05). Metformin 0.1-10 mM inhibited interleukin-8 release by 20-50% (p < 0.05) and mRNA expression by 20-90% (p < 0.05). However, ETYA did not effect the production of interleukin-8 in the adipose tissue. In conclusion, we demonstrate the ability of two anti-diabetic compounds to decrease the release of interleukin-8 from human adipose tissue in vitro. These findings open the possibility that the beneficial effects on cardiovascular risk-factors of these anti-diabetic compounds might involve a reduction in the interleukin-8 produced in human adipose tissue.

5,8,11,14-Eicosatetraynoic Acid↗
PubMedDate not supplied

Infrared analysis for determining macronutrients in human milk.

Infrared (IR) analysis is widely used for routine analysis of cow milk in dairies. The aim of this study was to evaluate the precision and accuracy of an IR analyzer (Milko-scan 104) for measuring protein, fat, carbohydrate, and, indirectly, the energy content of human milk. The results of the IR analysis were compared with those of the following reference methods: protein--Kjeldahl (nitrogen minus nonprotein nitrogen); fat--Roese Gottlieb; carbohydrate--lactose enzymatic assay; energy--bomb calorimetry. The precision (repeatability coefficient of variation) of the IR results was high for all four components: protein 0.4%, fat 1.0%, carbohydrate 0.2%, and energy 0.1%. There was a close linear covariation between IR results and reference results. [Protein content was determined with an error (SD) of 0.01 g/100 ml and fat with an error of 0.03 g/100 ml.] The covariation between IR carbohydrate results and the results of the lactose assay was poor, probably because the oligosaccharides in the milk were included in the results from the IR analysis and not in the results from the lactose assay. IR analysis is a valuable method in research, especially in epidemiological surveys, in which large numbers of samples are analyzed, and for continuous monitoring of the nutritional value of human milk in milk banking programs.

Humans↗
PubMedDate not supplied

Pharmacology of mesoionic oxatriazole derivatives in blood, cardiovascular and respiratory systems.

Mesoionic oxatriazole derivatives were synthetized by GEA LTD1. The GEA compounds (GEAC) constitute a new class of NO-donors, some of which stimulate selectively guanylate cyclase abiding either platelets or leukocytes or lung tissues. In consequence, some of GEAC are potent anti-platelet, fibrinolytic, thrombolytic or broncholytic agents, both in vitro and in vivo. GEAC synergize with prostacyclin in their thrombolytic actions. They also suppress the release of histamine and leukotriene B4, and prevent degranulation of granulocytes. Methylene blue reduces, and zaprinast augments their pharmacological effects. It is suggested that within a series of the newly synthetized GEA compounds there are likely to be found potential candidates for treating either thrombotic or asthmatic disorders.

Animals↗