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Biomedical subjects

J Bülow

Publications and source records attributed to J Bülow.

At least 55 records · Page 3Linked to original sources

Glucose metabolism in chronic diabetic foot ulcers measured in vivo using microdialysis.

Ten subjects with diabetes mellitus and unilateral chronic foot ulcer were investigated. Local tissue concentrations of glucose and lactate were measured using the microdialysis method at a distance of 0.5-1 cm from the edge of the ulcer and in normal skin in the contralateral foot. Subcutaneous blood flow in the area investigated was measured using the 133Xewashout technique. The interstitial glucose concentration in the ulcer was found to be lower than in intact skin (8.0 +/- 1.0 mmol l-1 vs. 8.5 +/- 1.1 mmol l-1) (P < 0.02), and the interstitial lactate concentration was higher in the ulcer than in intact skin (3.2 +/- 0.2 mmol l-1 vs. 2.1 +/- 0.3 mmol l-1) (P < 0.01). The subcutaneous blood flow was on average 40% higher in the ulcer than in the intact skin. The calculated local glucose uptake and lactate outputs were twofold higher in the ulcer than in the intact skin. However, the molar ratio between lactate output and glucose uptake was approximately two, both in the ulcer and in the intact skin, indicating that the glucose metabolism was qualitatively the same in the two regions.

Aged↗

Fat metabolism in formerly obese women.

An impaired fat oxidation has been implicated to play a role in the etiology of obesity, but it is unclear to what extent impaired fat mobilization from adipose tissue or oxidation of fat is responsible. The present study aimed to examine fat mobilization from adipose tissue and whole body fat oxidation stimulated by exercise in seven formerly obese women (FO) and eight matched controls (C). Lipolysis in the periumbilical subcutaneous adipose tissue, whole body energy expenditure (EE), and substrate oxidation rates were measured before, during, and after a 60-min bicycle exercise bout of moderate intensity. Lipolysis was assessed by glycerol release using microdialysis and blood flow measurement by 133Xe clearance technique. The FO women had lower resting EE than C (3.77 +/- 1.01 vs. 4.88 +/- 0.74 kJ/min, P < 0.05) but responded similarly to exercise. Adipose tissue glycerol release was twice as high in FO than in C at rest (0.455 +/- 0.299 vs. 0.206 +/- 0.102 mumol.100 g-1.min-1, P < 0.05) but increased similarly in FO and C in response to exercise. Despite higher plasma nonesterified fatty acids (NEFA) in FO (P < 0.001), fat oxidation rates during rest and recovery were lower in FO than in C (1.32 +/- 0.84 vs. 3.70 +/- 0.57 kJ/min, P < 0.02) and fat oxidation for a given plasma NEFA concentration was lower at rest (P < 0.001) and during exercise (P = 0.01) in the formerly obese group. In conclusion, fat mobilization both at rest and during exercise is intact in FO, whereas fat oxidation is subnormal despite higher circulation NEFA levels. The lower resting EE and the failure to use fat as fuel contribute to a positive fat balance and weight gain in FO subjects.

Adipose Tissue↗

Desensitization of human adipose tissue to adrenaline stimulation studied by microdialysis.

1. Desensitization of fat cell lipolysis to catecholamine exposure has been studied extensively in vitro but only to a small extent in human adipose tissue in vivo. 2. We measured interstitial glycerol concentrations by microdialysis in subcutaneous, abdominal adipose tissue in healthy humans during intravenous adrenaline infusion for three 35 min periods with 30 min breaks in between. Local blood flow, interstitial adrenaline and arterial glycerol concentrations were also measured. Adrenaline was infused to result in either a high, a low and a high arterial concentration (5.8, 3.1 and 5.6 nM, respectively) or a low, a high and a low concentration (2.5, 4.6 and 2.6 nM, respectively) in order to examine both desensitization and the dose dependency of adipose tissue lipolysis to adrenaline. 3. Adipose tissue lipolysis was calculated and was found to vary directly with arterial adrenaline concentration. However, lipolytic responses to adrenaline decreased markedly during repeated stimulation at a given concentration. Further, arterial glycerol and free fatty acid concentrations varied directly with arterial adrenaline concentrations and showed reduced responses upon repeated exposure. 4. The increase in adipose tissue blood flow in response to adrenaline was also reduced by prior adrenaline exposure, but no consistent desensitization could be demonstrated for whole-body energy expenditure, blood pressure and heart rate. 5. In the basal state, arterial plasma and interstitial adrenaline concentrations did not differ. During perturbations of arterial adrenaline concentrations, changes in interstitial concentrations were highly reproducible but smaller than changes in arterial concentrations. 6. In conclusion, in vivo adrenaline-mediated adipose tissue lipolysis and blood flow increments are desensitized by prior adrenaline exposure.

3-Hydroxybutyric Acid↗

Gentamicin concentrations in human subcutaneous tissue.

Wound infections frequently originate from the subcutaneous tissue. The effect of gentamicin in subcutaneous tissue has, however, normally been evaluated from concentrations in blood or wound fluid. The aim of the present study was to investigate the pharmacokinetic properties of gentamicin in human subcutaneous adipose tissue by a microdialysis technique. Seven healthy young volunteers each had four microdialysis probes placed in the fat (subcutaneous) layer of the abdominal skin. After the administration of a 240-mg gentamicin intravenous bolus, consecutive measurements of the drug concentrations in serum and subcutaneous interstitial fluid were obtained simultaneously for 6 h. The tissue gentamicin concentration peaked after 10 to 30 min. The peak concentration in the tissue was 6.7 +/- 2.0 mg.liter-1 (standard deviation), equivalent to 39.1% of the peak concentration in serum. The area under the concentration-versus-time curve for the first 6 h in the tissue was 1,281 +/- 390.0) mg.min liter-1, equivalent to 59.7% of the area under the concentration-versus-time curve in serum. It is concluded that the microdialysis technique can be used to make dynamic and quantitative measurements of the gentamicin concentration in human subcutaneous tissue. In this adipose tissue, the peak concentrations of gentamicin were approximately seven times the MIC for Pseudomonas aeruginosa and 33 times the MIC for Staphylococcus aureus after the administration of an intravenous bolus of 240 mg, indicating the presence of sufficient concentrations in the adipose tissue to be effective against common bacteria.

Adipose Tissue↗

Persistent resetting of the cerebral oxygen/glucose uptake ratio by brain activation: evidence obtained with the Kety-Schmidt technique.

Global cerebral blood flow (CBF), global cerebral metabolic rates for oxygen (CMRO2), and for glucose (CMRglc), and lactate efflux were measured during rest and during cerebral activation induced by the Wisconsin card sorting test. Measurements were performed in healthy volunteers using the Kety-Schmidt technique. Global CMRO2 was unchanged during cerebral activation, whereas global CBF and global CMRglc both increased by 12%, reducing the molar ratio of oxygen to glucose consumption from 6.0 during baseline conditions to 5.4 during activation. Data obtained in the period following cerebral activation showed that the activation-induced resetting of the relation between CMRglc and CMRO2 persisted virtually unaltered for > or = 40 min after the mental activation task was terminated. The activation-induced increase in cerebral lactate efflux measured over the same time period accounted for only a small fraction of the activation-induced excess glucose uptake. These data confirm earlier reports that brain activation can induce resetting of the cerebral oxygen/glucose consumption ratio, and indicate that the resetting persists for a long period after cerebral activation has been terminated and physiologic stress indicators returned to baseline values. Activation-induced resetting of the cerebral oxygen/glucose uptake ratio is not necessarily accounted for by increased lactate production from nonoxidative glucose metabolism.

Adult↗

Glucose-induced thermogenesis in splanchnic and leg tissues in man.

1. Fourteen healthy subjects were investigated before and for 4 hours after oral intake of 75 g of glucose (n = 8) or tap water (n = 6). Whole-body energy expenditure was measured by an open-circuit ventilated hood system. Blood samples for determination of oxygen, carbon dioxide, glucose and lactate were taken from an artery, a hepatic vein and a femoral vein. Blood flow in the splanchnic region was measured by constant infusion of Indocyanine Green. Leg blood flow was measured by venous occlusion strain-gauge plethysmography. Oxygen uptake and carbon dioxide output in the splanchnic and leg tissues were calculated as the product of blood flow and arteriovenous differences in oxygen or carbon dioxide concentrations. Net exchanges of glucose and lactate across the splanchnic and leg tissues were calculated as the product of blood flow and arteriovenous differences in whole-blood glucose or lactate concentrations. 2. Splanchnic oxygen uptake had a biphasic course with an initial increase from 2.35 +/- 0.88 (SD) mmol/min to 2.85 +/- 1.20 mmol/min 30 min after the glucose intake (P < 0.005) and a later decrease below the basal value to around 2.02 mmol/min 90-180 min after the glucose intake (P < 0.05). The integrated increase in the splanchnic oxygen uptake during the 4 h after the glucose intake was -32.6 +/- 49.7 mmol/240 min. Leg oxygen uptake increased from 4.3 +/- 1.4 mumol min-1 100 g-1 to 7.0 +/- 3.2 mumol min-1 100 g-1 90 min after the glucose intake (P < 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Effect of training on epinephrine-stimulated lipolysis determined by microdialysis in human adipose tissue.

Trained humans (Tr) have a higher fat oxidation during submaximal physical work than sedentary humans (Sed). To investigate whether this reflects a higher adipose tissue lipolytic sensitivity to catecholamines, we infused epinephrine (0.3 nmol.kg-1.min-1) for 65 min in six athletes and six sedentary young men. Glycerol was measured in arterial blood, and intercellular glycerol concentrations in abdominal subcutaneous adipose tissue were measured by microdialysis. Adipose tissue blood flow was measured by 133Xe-washout technique. From these measurements adipose tissue lipolysis was calculated. During epinephrine infusion intercellular glycerol concentrations were lower, but adipose tissue blood flow was higher in trained compared with sedentary subjects (P < 0.05). Glycerol output from subcutaneous tissue (Tr: 604 +/- 322 nmol.100 g-1.min-1; Sed: 689 +/- 203; mean +/- SD) as well as arterial glycerol concentrations (Tr: 129 +/- 36 microM; Sed: 119 +/- 56) did not differ between groups. It is concluded that in intact subcutaneous adipose tissue epinephrine-stimulated blood flow is enhanced, whereas lipolytic sensitivity to epinephrine is the same in trained compared with untrained subjects.

3-Hydroxybutyric Acid↗

Inter-relationships between single carbon units' metabolism and resting energy expenditure in weight-losing patients with small cell lung cancer. Effects of methionine supply and chemotherapy.

The one-carbon unit metabolism was investigated in 8 weight-losing patients with small cell carcinoma of the lung (SCLC). At diagnosis, 6 of the 8 patients had elevated formiminoglutamic acid (FIGLU) excretion after a histidine load, suggesting a lack of one-carbon units. In accordance, a significant decrease of FIGLU excretion was observed in the patients after oral administration of DL-methionine for 4 days. The elevated FIGLU excretion was positively correlated to weight loss prior to diagnosis and negatively correlated to serum albumin at time of diagnosis. After 3 months of combination chemotherapy, FIGLU excretion was reduced in all patients except 1, who had progressive disease. Despite the elevated FIGLU excretions, all patients had normal blood folate levels. The resting energy expenditure (REE) was recorded in 7 patients, and a significant, positive correlation was observed between pretreatment FIGLU excretion and REE, although the REE measured in this group of patients was within the normal range. These data demonstrate an increased demand of "active" one-carbon units in energy consumption in a group of weight-losing cancer patients. The one-carbon unit deficit was reconditioned by oral administration of the one-carbon unit donor DL-methionine.

Aged↗

Insulin sensitivity in post-obese women.

1. Both increased and decreased sensitivity to insulin has been proposed to precede the development of obesity. Therefore, insulin sensitivity was measured during a 2 h hyperinsulinaemia (100 m-units min-1 m-2) euglycaemic (4.5 mmol/l) glucose clamp combined with indirect calorimetry in nine weight-stable post-obese women and in nine matched control women preceded by 12 h fasting after 48 h on a standardized diet. 2. Both glucose disposal rate (post-obese women, 9.5 +/- 2.2 mg min-1 kg-1, control women, 11.2 +/- 1.4 mg min-1 kg-1, not significant) and glucose oxidation (3.6 +/- 0.5 mg min-1 kg-1 versus 4.0 +/- 0.7 mg min-1 kg-1, not significant) were similar in the two groups during the last 30 min of the clamp. Lipid oxidation also decreased similarly during the clamp in the post-obese women (from 30.4 +/- 12 to 2.0 +/- 7 J min-1 kg-1) and in the control women (from 33.6 +/- 11 to 5.4 +/- 8 J min-1 kg-1, not significant). Basal plasma concentrations of free fatty acids were similar, but at the end of the clamp free fatty acids were lower in the post-obese women than in the control women (139 +/- 19 and 276 +/- 48 mumol/l, P = 0.02). 3. We conclude that the insulin sensitivity of glucose metabolism is unaltered in the post-obese state. The study, however, points to an increased antilipolytic insulin action in post-obese subjects, which may favour fat storage and lower lipid oxidation rate postprandially.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Glucose-induced thermogenesis in patients with small cell lung carcinoma. The effect of acute beta-adrenergic inhibition.

Seven patients with histologically verified small cell lung carcinoma were given an oral glucose load of 75 g on two occasions to examine the effect of glucose on whole body and forearm thermogenesis with and without acute beta-adrenergic inhibition with propranolol. Whole body energy expenditure was measured by the open circuit ventilated hood system. Forearm blood flow was measured by venous occlusion strain-gauge plethysmography. The uptake of oxygen in the forearm was calculated as the product of the forearm blood flow and the difference in arteriovenous oxygen concentration. The glucose-induced thermogenesis in the 120 min following the glucose load was significantly reduced by beta-adrenergic inhibition with approximately 50% from 63.9 +/- 5.8 kJ 120 min-1 (mean +/- SE) to 27.8 +/- 9.8 kJ 120 min-1 (P < 0.01). Almost the entire reduction took place from 60 to 120 min (P < 0.005). The integrated glucose-induced forearm oxygen uptake in the period 60-120 min following the glucose load was significantly reduced after beta-adrenergic inhibition from 103 +/- 28 mumol 100 g-1 60 min-1 to 29 +/- 29 mumol 100 g-1 60 min-1 (P < 0.05). The noreadrenaline concentration in the arterial blood was not increased in the baseline period compared to healthy elderly; it increased following the glucose load while there was no demonstrable increase in adrenaline concentration in the two experiments. It is suggested that these patients have increased sensitivity of the beta-adrenergic receptors and an early facultative component of the glucose-induced thermogenesis in part takes place in the forearm.

Aged↗

Adipose tissue metabolism in humans determined by vein catheterization and microdialysis techniques.

A technique for catheterization of a vein draining abdominal subcutaneous tissue and a microdialysis technique that allows measurements of intercellular water concentrations in adipose tissue in humans have recently been described. In the present study, we compare the two techniques during an oral glucose load. In addition a technique using microdialysis for measurement of tissue oxygen and carbon dioxide tensions is described. Microdialysis and vein catheterization were performed in the same region on the abdomen, and the subcutaneous adipose tissue blood flow was measured by the local 133Xe washout method. The results show that subcutaneous adipose tissue gas tensions are on level with gas tensions measured in abdominal venous blood. Comparison of metabolite concentrations measured in the venous blood and venous blood concentrations calculated from microdialysis data shows that there is good agreement between the concentrations obtained by the two techniques with respect to glucose and glycerol, whereas lactate concentrations are very different. With regard to substrate fluxes calculated by Fick's principle, the catheterization technique is probably the most reliable, considering the numerous assumptions on which calculations of venous concentrations from microdialysis data are based. Advantages and disadvantages of the two techniques are discussed.

Abdomen↗

Glucose-induced thermogenesis in patients with small cell lung carcinoma. Before and after inhibition of tumour growth by chemotherapy.

Seven weight-losing patients with histologically verified small cell lung carcinoma were given an oral glucose load of 75 g before and at least 3 weeks after the end of chemotherapy to examine the effect of glucose on whole body and skeletal muscle thermogenesis before and after reduction of tumour. Whole body energy expenditure was measured by the open circuit ventilated hood system. Forearm blood flow was measured by venous-occlusion strain-gauge plethysmography. The uptake of oxygen in skeletal muscle was calculated as the product of the forearm blood flow and the difference in a-v oxygen concentration. Whole body resting energy expenditure (REE) did not increase, it was 4.4 +/- 0.3 kJ min-1 (mean +/- SE) before chemotherapy and 4.4 +/- 0.2 kJ min-1 after chemotherapy. The glucose-induced thermogenesis in the 180 min following the glucose load was 93.6 +/- 9.9 kJ 180 min-1 before chemotherapy. This is significantly increased compared to that found in a healthy control group (74.7 +/- 4.8 kJ 180 min-1, P < 0.02). The glucose-induced thermogenesis was significantly reduced to 47.7 +/- 10.2 kJ 180 min-1 (P < 0.05) after chemotherapy. The oxygen uptake in resting skeletal muscles was 6.9 +/- 0.3 mumol 100 g-1 min-1 before chemotherapy and 7.0 +/- 0.7 mumol 100 g-1 min-1 after chemotherapy. This did not increase during the first 90 min following the glucose load in either investigations. In the period 90-180 min following the glucose load, the oxygen uptake was significantly increased before chemotherapy as compared to after chemotherapy, which suggests that the reduced whole body thermogenesis after chemotherapy in part was due to reduced skeletal muscle thermogenesis.

Adult↗

Localization of thermogenesis induced by single infusion of ephedrine in dog.

The localization of the thermogenic effect of ephedrine (1 mg.kg-1 infused intravenously over 10 min.) was studied in 6 fasted dogs anaesthetized with etorfin-acepromazin-N2O. Three experiments were performed in each animal to determine the effect of ephedrine on a) splanchnic oxygen uptake, b) lower leg oxygen uptake and c) the work of the heart. In all experiments whole body oxygen uptake was monitored. Following ephedrine administration the following significant changes were seen as whole body oxygen uptake increased 16%, and splanchnic and lower leg oxygen uptakes increased respectively from 38.4 to 42.3 and from 7.3 to 12.1% of the whole body control oxygen uptake. The pressure-volume work of the heart more than doubled. Significant changes were also seen in mean arterial blood pressure, pulse rate, cardiac output, splanchnic blood flow, and haematocrit and haemoglobin concentration. Plasma glycerol and free fatty acid concentrations increased after ephedrine, and the effects were not elicited by circulating catecholamines.

Animals↗

Local forearm and whole-body respiratory quotient in humans after an oral glucose load: methodological problems.

The effects of an oral glucose load of 75 g on the local forearm and whole-body energy thermogenesis were measured in normal subjects during the 4 h after the glucose intake. Simultaneous assessment of substrate metabolism in the forearm was performed. Energy expenditure (EE) increased after the glucose load and had not returned to baseline level at the end of the experiment. Whole-body respiratory quotient (RQ) was, on average, 0.80 (SD 0.05) in the baseline condition and increased to a maximum of 0.91 (0.03) and then decreased to baseline level at the end of the experiment. The local forearm oxygen uptake increased 30 min after the glucose intake and remained elevated during the rest of the experiment. The carbon dioxide output from the forearm did not increase before 90 min after the glucose load. Consequently the local forearm RQ decreased significantly from a baseline value of 0.86 (0.17) to 0.63 (0.17) 30 min after the glucose load (P < 0.05). Ninety min after the glucose load RQ increased to a maximum level at 0.95 (0.22) and decreased then gradually to baseline level. The experiments emphasize several methodological problems in the measurement of local forearm RQ. The whole-body RQ and local forearm RQ are not significantly different in the fasting state. The finding of a decrease in local forearm RQ below 0.70 30 min after the glucose load probably indicates a non-steady state in the carbon dioxide exchange. Thus, indirect calorimetry cannot be applied locally during short time periods.

Adult↗

Contribution of skeletal muscle and adipose tissue to adrenaline-induced thermogenesis in man.

Elevated plasma adrenaline is known to increase whole body energy expenditure. We studied the thermogenic effect and the effects on substrate utilization in man during infusion of adrenaline. Two series were performed: in one series skeletal muscle metabolism was investigated and in another series subcutaneous adipose tissue metabolism was investigated. In both series Fick's principle was applied. Intravenous infusion increased blood flow, glucose uptake and oxygen uptake in both skeletal muscle and adipose tissue. It is concluded that skeletal muscle contributes about 40% and adipose tissue about 5% of the whole body adrenaline-induced thermogenesis.

Adipose Tissue↗

Microdialysis of the interstitial water space in human skin in vivo: quantitative measurement of cutaneous glucose concentrations.

The purpose of this study was to evaluate the usefulness of a microdialysis technique for measurement of substances in the interstitial water space in intact human skin. Glucose was selected to validate the method. The cutaneous glucose concentration was measured by microdialysis and compared to that in venous blood. Single dialysis fibers (length 20 mm, 2,000 Da molecular weight cutoff) were glued to nylon tubings and inserted in forearm skin by means of a fine needle. Dialysis fibers were inserted in duplicate. Seven subjects were investigated after an overnight fast. Intradermal position of the dialysis probes was established by C-mode ultrasound scanning. The implantation trauma lasted 90-135 min as measured by laser Doppler flowmetry. Each dialysis fiber was calibrated in vivo by perfusing it with four to five different glucose concentrations. The perfusion rate was 3 microliters/min. Regression analysis of the calibration curves yielded the relative in vivo recovery of glucose. The skin glucose concentration was calculated as that particular perfusate glucose concentration that resulted in no net glucose transport across the dialysis membrane. Correlation coefficient of the regression lines was 0.93 +/- 0.03 (mean +/- SEM). After the injection trauma had vanished, recovery was 20.5 +/- 0.7%. Coefficient of variation (CV) on recovery was 10.9%. The cutaneous glucose concentration was 99.1 +/- 1.8% of the glucose concentration in venous plasma water (CV 4.1%). These findings suggest that the microdialysis technique accurately and precisely can reflect biochemical events in the interstitial water space in human skin in vivo.

Adult↗