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Biomedical subjects

J Madsen

Publications and source records attributed to J Madsen.

At least 109 records · Page 6Linked to original sources

Reversibility of the effects on local circulation of high lipid concentrations in blood.

Regional perfusion and vascular resistance were examined in different tissues with the radioactive microsphere technique in Göttingen minipigs before, during and after treatment with Intralipid and heparin. This treatment led to an increase in the free fatty acid/albumin molar ratio from 0.39 +/- 0.23 to 3.43 +/- 1.37. Concomitantly a decrease in regional perfusion and an increase in regional vascular resistance was found in skin, adipose tissue, skeletal muscle, kidney, the gastro-intestinal tract, the thyroid and pancreas, while heart and liver showed vasodilatation. The vascular effects were fully reversible when the free fatty acid/albumin molar ratio had normalized. This vascular effect of lipid emulsions has to be considered when patients are treated with parenteral nutrition.

Adipose Tissue↗

Decreased blood perfusion in canine tibial diaphysis after filling with acrylic bone cement compared with inert bone wax.

Sixteen dogs had one tibia filled with acrylic PMMA bone cement and the opposite, control tibia filled with inert bone wax. After 1, 4, and 12 weeks, the blood perfusion in diaphyses was measured with Sc-46 labeled microspheres. The blood flow rates increased from 1 to 4 weeks and dropped to about the 1-week level after 12 weeks on both sides, with the acrylic side lower than the control side. On both sides, Disulphine Blue staining of the bones showed severe endosteal avascularity after 1 and 4 weeks and massive periosteal apposition after 4 and 12 weeks. The initial increase in blood flow is considered due to periosteal apposition, and the differences in blood flow rates are attributed to avascularity caused by the polymerization heat and toxicity of the acrylic cement.

Animals↗

Epinephrine mediates facultative carbohydrate-induced thermogenesis in human skeletal muscle.

The thermic effect of carbohydrate has a component mediated by the sympathoadrenal system but of unknown anatomical localization. We have studied the contribution of skeletal muscle to the thermic effect of a carbohydrate-rich natural meal (115 g of carbohydrate, approximately 80% of energy) by means of the forearm technique on two occasions, with and without intravenous beta-blockade with propranolol. The meal-induced thermogenesis was reduced from 9.6 to 7.1% by beta-blockade (P less than 0.04), the major difference was found 90 to 240 min after the meal. The postprandial increments in plasma glucose and lactate did not change by beta-blockade, but there was a trend toward a decreased insulin response (P = 0.06). The carbohydrate-induced increase in forearm oxygen consumption was reduced by 23% after beta-blockade (P less than 0.05), the entire difference being present 90-180 min postprandially and coinciding with the peak in arterial epinephrine. The present study provides evidence of a facultative thermogenic component in skeletal muscle, mediated by epinephrine via beta 2-adrenoreceptors. However, it also points to a nonmuscle component mediated through beta 1-adrenoceptors by norepinephrine released from the sympathetic nervous system. Consequently, the sympathoadrenal system seems to play a physiological role in the daily energy balance.

Adult↗

Influence of heliox, oxygen, and N2O-O2 breathing on N2 bubbles in adipose tissue.

Bubbles in rat adipose tissue were studied at 1 bar after decompression from an exposure to air at 3.3 bars (absolute) for 4 h. During air breathing the bubbles grew throughout the observation period. During heliox (80:20) breathing they shrank and eventually disappeared from view. If the breathing gas was changed from heliox back to air or to N2O-O2 (80:20) while the bubbles still had an appreciable size, they started growing again. If the change to N2O was done after or a few minutes before a bubble disappeared from view, it did not reappear. During breathing of 100% O2, most bubbles containing N2 initially grew and then maintained their size for a while before diminishing. However, some bubbles did not start shrinking during the 2-3-h observation period. The relevance of the findings to heliox treatment of CNS decompression sickness after air dives is discussed.

Adipose Tissue↗

Thought disorder and associative cognitive dysfunction in the first-degree relatives of adult schizophrenics. A reply to Romney.

Contrary to both theoretical and empirical findings, Romney equates associative cognitive dysfunction with other manifestations of thought disorder. Moreover, he overstates the case for the documentation of thought disorder in the families of schizophrenics. We discuss his reaction to Callahan and Saccuzzo in the context of four major issues. We conclude that the evidence for thought disorder in the families of schizophrenics is weak and inconclusive. We call for more rigorous research as well as the exploration of viable alternatives.

Adult↗

Gastric mucosal electrical potential difference and blood flow during high FFA/albumin ratios in anaesthetized Göttingen mini-pigs.

The gastric blood flow and the gastric mucosal potential difference (p.d.) was studied in anaesthetized Göttingen mini-pigs under normal conditions and during increased FFA/albumin ratios. The antrum mucosal p.d. was measured continuously with a newly developed intragastric microelectrode principle. The gastric blood flow was measured with the radioactive microsphere technique: at basal conditions, during high FFA/albumin ratios, and after normalization of the plasma lipids. The antrum p.d., expressed with gastric lumen negative, decreased during the increased FFA/albumin ratios; from -25 +/- 3 mV to -17 +/- 4 mV, (P less than 0.05). A further reduction to -12 +/- 3 mV (P less than 0.05) was observed during the normalization of the FFA/albumin ratios. The antrum and corpus mucosal blood flow values were reduced by 37 and 26% during the increased FFA/albumin ratios, and the gastric mucosal blood flow returned to initial values after normalization of the plasma lipids. The p.d. reduction during and after the increased FFA/albumin ratios could reflect a reduced active ion transport across the mucosa caused by a changed gastric mucosal metabolism.

Animals↗

Radioiodinated, photoactivatable phosphatidylcholine and phosphatidylserine: transfer properties and differential photoreactive interaction with human erythrocyte membrane proteins.

An isotopically labeled cross-linking reagent, succinimido 3-(3-[125I]iodo-4-azidophenyl)propionate, has been synthesized and coupled to 1-acyl-2-(aminocaproyl)phosphatidylcholine according to previously described procedures [Schroit, A. J., & Madsen, J. (1983) Biochemistry 22, 3617-3623]. 125I- and N3-labeled phosphatidylserine (125I-N3-PS) was produced from the phosphatidylcholine (PC) analogue by phospholipase D catalyzed base exchange in the presence of L-serine. These phospholipid analogues are photoactivatable, are labeled with 125I at high specific activity, completely incorporate into synthetic vesicles, and spontaneously transfer between membranes. When an excess of acceptor vesicles or red blood cells (RBC) was mixed with a population of donor vesicles containing the 125I-N3-phospholipids, approximately 40% of the analogues transferred to the acceptor population. After transfer in the dark to RBC, all of the 125I-N3-PC incorporated into the cells could be removed by washing with serum, whereas the 125I-N3-PS could not. After photolabeling of intact RBC, approximately 50% of the PC and 20% of the PS cross-linked to membrane proteins as determined by their insolubility in CHCl3/MeOH. Analysis of probe distribution by sodium dodecyl sulfate-polyacrylamide gel electrophoresis revealed that 125I-N3-PS preferentially labeled a Mr 30,000 peptide which contained approximately 30% of the protein-bound label.

Erythrocyte Membrane↗

Tissue/blood partition coefficients for xenon in various adipose tissue depots in man.

Tissue/blood partition coefficients (lambda) for xenon were calculated for subcutaneous adipose tissue from the abdominal wall and the thigh, and for the perirenal adipose tissue after chemical analysis of the tissues for lipid, water and protein content. The lambda in the perirenal tissue was found to correlate linearly to the relative body weight (RBW) in per cent with the regression equation lambda = 0.045 . RBW + 0.99. The subcutaneous lambda on the abdomen correlated linearly to the local skinfold thickness (SFT) with the equation lambda = 0.22 SFT + 2.99. Similarly lambda on the thigh correlated to SFT with the equation lambda = 0.20 . SFT + 4.63. It is concluded that the previously accepted lambda value of 10 is generally too high in perirenal as well as in subcutaneous tissue. Thus, by application of the present regression equations, it is possible to obtain more exact estimates of the adipose tissue blood flow measured with the 133Xe wash-out method.

Adipose Tissue↗

Impaired glucose-induced thermogenesis in skeletal muscle in obesity. The role of the sympathoadrenal system.

From a 7-day food recording in 29 morbidly obese patients two groups of six patients each were selected: a high-energy-intake group (HEI) and a low-energy-intake group (LEI). The groups were otherwise comparable. Five lean subjects served as controls for some observations. Oral glucose tolerance tests showed that all patients in the HEI group and the lean controls had normal glucose tolerance, whereas it was abnormal in all subjects in the LEI group. The fasting metabolic rate did not differ between the obese groups but was significantly lower in the lean group. The glucose-induced thermogenesis during 180 min expressed as a percentage of the energy content of the glucose load was lower in both obese groups compared with the lean controls (lean: +11.5 per cent, HEI: +5.3 per cent and LEI: -4.2 per cent, HEI vs lean: P = 0.04 and LEI vs lean: P = 0.005), and lower in the LEI group compared with the HEI group (P = 0.02). The integrated increase in leg oxygen consumption after glucose was also smaller in the LEI group than in the HEI group (15 +/- 269 vs 987 +/- 356 ml, P less than 0.05). The arterial noradrenaline response to glucose was significantly diminished in both obese groups compared with the lean controls. Glucose induced a similar increase in leg noradrenaline release in both obese groups, whereas the arterial adrenaline level was lower in the LEI group compared with the HEI group and with the lean controls (P = 0.04). Among the obese subjects the degree of glucose intolerance was inversely correlated with the post-glucose arterial adrenaline level (r = -0.55, and P = 0.04), and positively correlated with the fractional leg adrenaline extraction (r = 0.71, and P = 0.003). The results suggest that patients who are obese in spite of a fairly low energy intake have a reduced glucose-induced facultative thermogenesis, and that the defect is at least in part located in skeletal muscle. Since the sympathetic nervous system is partly responsible for the glucose-induced thermogenesis, the reduced thermogenic response in the obese patients may be due to an impaired activation of the sympathetic nervous system. It is hypothesized that the reduced arterial adrenaline level in the LEI group is caused by hyperglycaemic suppression of the adrenomedullary secretion and further that this may be a link connecting deterioration of glucose tolerance and a thermogenic defect in obesity.

Adrenal Glands↗

The effect of chronic ephedrine treatment on substrate utilization, the sympathoadrenal activity, and energy expenditure during glucose-induced thermogenesis in man.

Chronic ephedrine treatment of man has recently been found to enhance the thermogenic response to an acute dose of ephedrine. Conceivably, this sensitization to beta-adrenergic stimulation might also affect the facultative component of diet-induced thermogenesis. The glucose-induced thermogenesis (GIT) was studied in five healthy female subjects after 3 months of chronic peroral ephedrine treatment. Similar experiments 3 months after cessation of treatment served as controls. During chronic ephedrine treatment a sustained 10% elevation of the metabolic rate was found compared to that in the control study. Plasma epinephrine levels were increased 87% during treatment. These increases tended to be positively correlated (r = 0.54, P less than 0.07). GIT expressed as a percentage of the ingested energy load was unaltered during chronic ephedrine treatment compared with that in the control study (9.0% v 8.9%). The respiratory quotient (RQ) indicate that relatively more lipid was oxidized during chronic ephedrine treatment than in the control study. This change was observed in the fasting state as well as after glucose administration. Certain effects of ephedrine seems to be appropriate to a thermogenic drug for the treatment of obesity: A single dose of ephedrine stimulates thermogenesis, an effect that is enhanced during chronic treatment; Chronic treatment elevates the metabolic rate; and The substrate utilization is changed in favor of lipid oxidation.

Adult↗

A chronic sheep preparation for the study of drug pharmacokinetics in spinal and ventricular CSF.

We describe a sheep preparation utilizing chronic vascular and subarachnoid catheterization and ventriculocisternal perfusion. This preparation allows simultaneous, atraumatic sampling of plasma and CSF after drug administration by the intravenous, intracerebroventricular, or lumbar intrathecal (i.t.) routes in an unanesthesized animal. This sheep preparation provides a convenient means of studying the CSF distribution of exogenous and/or endogenous substances. During intravenous infusion at a rate of 2.2 micrograms/kg/min, morphine appears in cisternal CSF within 15 min. The steady-state plasma concentration and CSF flux (or appearance rate) of morphine was 0.037 and 0.009 micrograms/min, respectively. At steady state, 0.008% of the administered dose appears in CSF/min. The coadministration of morphine, methadone, and [14C]sucrose into the fifth lumbar subarachnoid space is associated with the simultaneous appearance of morphine and [14C]sucrose, but not methadone, in cisternal CSF. The ratio of [14C]sucrose to morphine increased by nearly sevenfold in cisternal CSF, indicating clearance of morphine relative to [14C]sucrose as the compounds ascend in the CSF axis. The simultaneous appearance of morphine and [14C]sucrose in cisternal CSF after lumbar subarachnoid administration indicates that morphine, like sucrose, is distributed within the CSF by bulk flow. This sheep preparation can be used to provide the quantitative data necessary for the development of pharmacokinetic-pharmacodynamic models that relate plasma and CSF concentrations of opiates to their pharmacological effects. These studies will help to provide the pharmacological rationale for the administration of opiates by novel routes for pain management in man.

Animals↗

Inhibition of fatty acid mobilization by arterial free fatty acid concentration.

Subcutaneous, inguinal adipose tissue from dogs was perfused with blood in which the free fatty acid (FFA) concentration was varied corresponding to FFA/albumin molar ratios between 1 and 6. Otherwise the composition of the perfusate was kept constant. In order to stimulate lipolysis, isoprenaline and theophyllamine were added to the perfusate. A raise in arterial FFA/albumin molar ratio was without influence on lipolysis (as reflected in the release of glycerol), but reduced the FFA release indicating an increased re-esterification. At FFA/albumin ratios above 3 a marked increase in vascular resistance was seen. This increase was partly reversible within the time of a perfusion. When lipolysis is stimulated in the intact organism, the effects of increasing arterial FFA/albumin ratio on re-esterification and vascular resistance may serve as feedback mechanisms regulating FFA mobilization.

Adipose Tissue↗