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Biomedical subjects

J Madsen

Publications and source records attributed to J Madsen.

At least 127 records · Page 7Linked to original sources
PubMed1986

Exercise-induced increase in dog adipose tissue blood flow before and after denervation.

Subcutaneous adipose tissue blood flow was examined during rest and exercise in the inguinal fat pads of four female dogs using the Xe wash-out technique. The experiments were performed before and after denervation of one of the pads. No difference between the resting flows in the two pads could be demonstrated either before or after denervation. The flow increased about two-fold on average from rest to exercise. This response was similar before and after denervation. It is concluded that direct sympathetic innervation is not involved in the regulation of adipose tissue blood flow during exercise.

Adipose Tissue↗
PubMed1986

Facultative thermogenesis induced by carbohydrate: a skeletal muscle component mediated by epinephrine.

In addition to the obligatory thermogenesis due to processing and storage, carbohydrate ingestion is accompanied by a facultative thermogenesis mediated by catecholamines via beta-adrenoceptors. The anatomical origin of facultative thermogenesis has hitherto not been determined. The possible involvement of skeletal muscle was examined in lean, healthy subjects by measuring the response in forearm oxygen consumption to an oral glucose load. The study demonstrates an early component of skeletal muscle thermogenesis coinciding with the local glucose uptake, followed by a late facultative thermogenesis. The arterial epinephrine concentration increased to a maximum of 200% above base-line values 4 h after glucose. This value greatly exceeds the physiological threshold for the thermogenic action of epinephrine. In forearm venous blood the corresponding increase in epinephrine was only approximately 50% due to enhanced peripheral extraction, which accompanies an increase in arterial epinephrine levels. Due to venous sampling previous studies have overlooked the magnitude of the late postglucose increase in arterial epinephrine, and its potential thermogenic effect has been disregarded. The facultative thermogenesis in skeletal muscle may be of importance for the regulation of body weight in humans.

Adult↗
PubMed1986

Neuropeptide investigations with an ovine surgical model.

An ovine surgical model for peptide investigations is presented. Techniques for exteriorization of the carotid artery, catheterization of the sagittal sinus, hypophysectomy via a transnasopharyngeal approach, and ventricular and cisternal cannulation in the sheep are employed within the model. Several experimental applications in neurosurgical research are presented.

Anesthesia↗
PubMed1985

Enhanced thermogenic responsiveness during chronic ephedrine treatment in man.

The thermogenic effect of a single oral dose of ephedrine (1 mg/kg body weight) was studied by indirect calorimetry in five women with 14% overweight before, during and 2 mo after 3 mo of chronic ephedrine treatment (20 mg, perorally, three times daily). Before treatment and 2 mo after its cessation a similar thermogenic response to ephedrine was observed. The total extra consumption of oxygen was 1.3 1 before and 1.2 1 after cessation of the chronic treatment. After 4 and 12 wk of treatment ephedrine elicited a more sustained response, the extra oxygen consumption in the 3 h following ephedrine intake being 7.0 and 6.9 1, respectively. The ratio of serum T3 to T4 increased significantly after 4 wk of treatment (15.6 +/- 1.3 vs 19.4 +/- 2.4; p less than 0.05), but decreased below the initial value after 12 wk treatment. The mean body weight was significantly reduced after 4 and 12 wk of treatment (2.5 and 5.5 kg, respectively). An improved capacity for beta-adrenergic induced thermogenesis may be useful in the treatment of obesity.

Adipose Tissue, Brown↗
PubMed1985

Vasoconstrictor effect of high FFA/albumin ratios in adipose tissue in vivo.

Subcutaneous or perirenal adipose tissue blood flow was measured with the 133Xe-washout technique before and after intravenous injection or infusion of Intralipid in six anesthetized, otherwise intact mongrel dogs. In four anesthetized mongrel puppies adipose tissue blood flow was measured with the radioactive microsphere method in seven different adipose tissue depots before a bolus injection of Intralipid and at the time after the injection when the thermogenic effect of the Intralipid was maximal. The results showed that the vascular resistance increased in all the examined adipose depots in adult as well as in young dogs after this treatment. The administration of Intralipid did not per se induce the vasoconstriction. The vasoconstriction took place simultaneously with increasing FFA/albumin molar ratios. The results support our previous findings in perfused fat pads that high molar FFA/albumin ratios increase vascular resistance in adipose tissue and they give further support to our suggestion that this vasoconstriction may be a link in a negative-feedback mechanism regulating FFA-mobilization in relation to FFA utilization.

Adipose Tissue↗
PubMed1985

Contribution of BAT and skeletal muscle to thermogenesis induced by ephedrine in man.

This investigation was performed to examine the role of brown adipose tissue (BAT) in thermogenesis induced by ephedrine in man. Light microscopy of biopsies from necropsy cases showed BAT to occur most frequently in the perirenal fat. Perirenal BAT thermogenesis was investigated in five lean men before and during stimulation with 1 mg ephedrine orally X kg body wt-1. Perirenal BAT thermogenesis was assessed by continuous measurements of local temperature and blood flow with the 133xenon clearance method. In the same study the effect of ephedrine on skeletal muscle oxygen consumption was estimated by measurements of leg blood flow and arteriovenous oxygen difference. The perirenal adipose tissue blood flow increased approximately twofold, whereas the local temperature increased approximately 0.1 degrees C on an average. Assuming that man possesses 700 g of BAT with a similar thermogenic capacity, this tissue contributed only 10 ml X min-1 to the 40 ml X min-1 increase in oxygen consumption in the subject whose perirenal BAT showed the most pronounced response to ephedrine. The leg oxygen consumption increased on an average 60% after ephedrine. By extrapolation of this value to whole body skeletal muscle, approximately 50% of the increase in oxygen consumption induced by ephedrine may take place in skeletal muscle. It is concluded that skeletal muscle is a tissue of importance with respect to the thermogenic effect of sympathomimetics in man, whereas the results do not support a major role for perirenal BAT.

Adipose Tissue, Brown↗
PubMed1984

Interscapular brown adipose tissue blood flow in the rat. Determination with 133xenon clearance compared to the microsphere method.

The xenon clearance method was adapted to continuous measurement of interscapular brown adipose tissue (ISBAT) blood flow in anesthetized rats. The ISBAT-blood partition coefficient for xenon was determined to 3.6 ml X g-1. The blood flow values obtained by Xe clearance were compared with flow values obtained concomitantly by the microsphere technique in 17 cold acclimated rats, at ISBAT blood flows between 0.1 and 6 ml X g-1 X min-1. Variations in blood flows were obtained by infusion of noradrenaline at different rates. The blood flow values obtained from the xenon clearance method showed a close correlation to the blood flow values determined with microspheres. Y = 0.98. X + 0.15 (r = 0.96, P less than 0.001). The Xe clearance method has the advantages compared to the microsphere technique that it permits continuous monitoring of the blood flow and does not require the sacrifice of the animal.

Adipose Tissue, Brown↗
PubMed1984

Ephedrine-induced thermogenesis in man: no role for interscapular brown adipose tissue.

The warmest interscapular skin areas were located by thermography in six healthy subjects during ephedrine-induced thermogenesis. In these interscapular areas, and in lumbar control areas, the skin temperature, subcutaneous temperature and adipose tissue blood flow were measured before and during ephedrine-induced thermogenesis. The skin and subcutaneous temperatures increased in the interscapular area as well as in the lumbar area, by about 0.7-1.2 degrees C. The interscapular skin temperature remained about 1 degree C higher than the lumbar; the subcutaneous temperatures in the two areas were identical during the experiments. Although the interscapular subcutaneous adipose tissue blood flow increased about sixfold and the lumbar increased twofold, the absolute flows were higher in the lumbar area. The oxygen uptake increased to a maximum of 30% above control level. Plasma glucose and glycerol concentrations remained unchanged, and plasma non-esterified fatty acids, lactate and noradrenaline concentrations increased slightly but significantly. Biopsies taken from the hot interscapular areas did not contain brown adipose tissue. It is concluded that the high interscapular skin temperature may be due to a lower insulating fat thickness and that the increases in skin and subcutaneous temperatures during ephedrine-induced thermogenesis are caused by an increased blood flow. These observations weigh against the hypothesis that the interscapular temperature increase is due to functional, interscapular brown adipose tissue.

Adipose Tissue↗
PubMed1984

The recognition of red blood cells by macrophages: role of phosphatidylserine and possible implications of membrane phospholipid asymmetry.

The recognition of phosphatidylserine (PS) by macrophages was investigated using inside-out (IO) red blood cell (RBC) ghosts and RBC displaying PS in their surface membranes. This was accomplished by employing unmodified pathologic sickle RBC which contain endogenous PS in their outer membrane leaflet, and RBC modified by the transfer of an exogenous fluorescent PS analog. Proper insertion of exogenous PS was confirmed by monitoring the degree to which cell-associated lipid fluorescence was dequenched following transfer of 1-acyl-2-[(N-4-nitro-benzo-2-oxa-1,3 diazole) aminocaproyl] phosphatidylserine (NBD-PS) from a population of self-quenched donor vesicles. Inside-out RBC ghosts were endocytosed approximately 3 times faster than were right side-out control populations. Similarly, using NBD-PS vesicles at concentrations at which dilution of all the cell-associated analog in the recipient RBC could be unequivocally confirmed, we observed that the uptake of NBD-PS treated RBC by macrophages was significantly increased over that of control RBC populations. Fluorescence and electron microscopic observations revealed the formation of typical RBC-macrophage rosettes that were morphologically distinct from opsonized RBC-macrophage rosettes. Enhanced RBC binding to macrophages was also obtained with deoxygenated reversibly sickled cells (RSC); the enhancement correlated with increased exposure of outer leaflet PS in these cells. These findings suggest that PS is recognized by macrophages and that its exposure in the outer leaflet of RBC may have significant pathophysiologic implications.

4-Chloro-7-nitrobenzofurazan↗
PubMed1984

Development of biological diversity and susceptibility to chemotherapy in murine cancer metastases.

We studied the development of biological heterogeneity in a spontaneous melanoma metastasis of clonal origin as demonstrated by karyotypic analysis. The metastatic potential and sensitivity to different chemotherapeutic agents varied both among and within clones of this metastasis isolated either in vitro or in vivo. This finding indicates that, even within a metastasis of clonal origin, cellular heterogeneity for chemotherapy or metastatic potential can develop rapidly and provides a mechanism for the emergence of resistance to therapy. Since most cancer deaths result from metastases that do not respond to treatment, the implications of these findings for the treatment of cancer are clear. Treatment modalities must be designed that circumvent the biological heterogeneity that can develop rapidly within each metastasis and among metastases.

Animals↗
PubMed1983

Effects of physical activity and immobilization on plasma digoxin concentration and renal digoxin clearance.

Plasma digoxin concentration and renal digoxin clearance were determined during 2 hr of normal physical activity and during 2 hr of complete immobilization in eight healthy subjects on steady-state digoxin dosing. Mean plasma digoxin concentration rose from 0.64 +/- 0.13 ng/ml during physical activity to 1.04 +/- 0.19 ng/ml (63%) after 2 hr of rest. Resumption of physical activity resulted in gradual decline of plasma digoxin, and subsequent strenuous exercise reduced the value to preimmobilization level. Mean renal digoxin clearance was reduced from 168.4 +/- 18.7 ml/min during physical activity to 137.2 +/- 32.7 ml/min during rest whereas creatinine clearance was unchanged. The rise in plasma digoxin during rest is presumed to be due to changes in the binding of the drug to tissues such as skeletal muscles. Our findings indicate that attention should be given to the state of physical activity when kinetic studies are performed or when digoxin therapy is monitored by means of plasma digoxin analysis.

Adult↗
PubMed1983

Effects of glucose, insulin and nicotinic acid on adipose tissue blood flow in rats.

Adipose tissue blood flow (ATBF) was examined in rat parametrial fat by the 133-Xe elimination method. Intravenous infusion of glucose to fed rats resulting in blood glucose concentrations of 10-12 mmol X 1(-1) caused a significant reduction in ATBF (-37%). Similar infusions to 48 hour fasted rats had no consistant effect on ATBF. Glucose infusion caused a significant rise in plasma insulin concentrations in both fed and fasted animals, although the average concentration in fasted rats given glucose did not exceed the control value in fed animals. Insulin added to the glucose infusion caused a similar reduction in ATBF in fasted animals as that seen after glucose alone in fed animals (-38%). Guinea pig anti insulin serum administered intravenously to fed rats elicited an increase in blood glucose concentrations similar to that seen after glucose infusion, but was without effect on ATBF. These results suggest that the effect of glucose on ATBF is secondary to a release of insulin resulting in plasma levels above those found in fed control rats. Infusion of nicotinic acid also reduced ATBF without influencing blood glucose concentration and in spite of insulin concentrations lower than in fed control rats. Since both insulin and nicotinic acid inhibit the formation of c-AMP in adipocytes, it is hypothesized that both compounds decrease ATBF by decreasing the release of the vasodilator adenosine from the cells.

Adipose Tissue↗
PubMed1983

Selective delivery of drugs encapsulated in liposomes: natural targeting to macrophages involved in various disease states.

In recent years, a considerable effort has been made to promote the use of liposomes as potential carriers for systemically administered chemotherapeutic agents. It is our belief that much of this proselytizing has ignored the normal and unavoidable fate of systemically administered liposomes, which is clearance by the reticuloendothelial system. Rather than attempting to avoid this phenomenon, we suggest that this occurrence could be advantageous for the selective delivery of agents to cells of the monocyte-macrophage series involved in various disease states.

Humans↗
PubMed1981

Influence of blood flow on fatty acid mobilization form lipolytically active adipose tissue.

Subcutaneous, ingvinal adipose tissue from dogs was perfused with blood to which had been added isoprenaline and theophyllamine in order to stimulate lipolysis. The supply of free fatty acid (FFA) carrier to the tissue was varied either by variations in the rate of blood flow or by changes in the albumin concentration of the perfusing blood at constant flow rate. The net production of FFA from the tissue was found to depend on the supply of carrier over a range from 0.1 -- 12 mumoles of albumin x 100 g tissue-1 x min-1. The corresponding molar FFA/albumin ratios in adipose venous blood varied between 12.1 and 1.2. The changes in FFA production appeared to be due to varying degrees of reesterification rather than changes in the rate of lipolysis. The findings suggest that the increase in adipose tissue blood flow demonstrated during various lipolytic conditions is of physiological importance by facilitating the removal of FFA from adipose tissue. Equilibration experiments showed the FFA binding capacity of both dog serum and human plasma to be above than calculated from the association constants of purified human albumin, suggesting the binding of FFA to other plasma carriers than albumin.

Adipose Tissue↗
PubMed1981

Electroencephalographical-anatomical correlation of brain tumours in infancy and childhood.

EEG correlated with anatomical aspects of 198 brain tumours in children gave the following results in hemispheric neoplasms: a rather precise location in 40% of the cases; lateralized in 42%; 14% showed only generalized anomalies and 4% were normal tracings. The findings depended on location and ICP condition, but not on neurological signs nor on histological nature. Basal-midline location (88 tumors) displayed 82.4% abnormal EEGs; 50% pointed to the more invaded hemisphere, mainly from the upper brain stem, ventricles and basal ganglia regions. Hypophyseal tumours gave 50% abnormalities with proved compression of the third ventricle, hypothalamus and cerebral peduncles. In posterior fossa tumours (60 cases), abnormalities are frequent (86.7%), but the localizing value of EEG is uncertain due to bisynchronous bursts mainly in the occipital region; 15% were lateralized with correlating asymmetrical location and/or growth of tumours. Differences compared to adult tumours are mentioned as specially influenced by maturational processes of the brain.

Adolescent↗