bluuebunny/crossref_metadata_2025_split huggingface dataset:
Metabolic Effects of Low-Dose Dopamine Infusion in Normal Volunteers
Authors: Regan Cathy J. , Duckworth R. , Fairhurst Judith A. , Maycock Paula F. , Frayn K. N. , Campbell I. T. 
Published: August 2015

1. Dopamine in 5% (w/v) d-glucose was infused into five healthy male volunteers at doses of 2, 5 and 10 μg min−1 kg−1 over three sequential periods of 45 min each.
2. Oxygen consumption, respiratory exchange ratio, blood glucose concentration and plasma levels of free fatty acids, glycerol, lactate, dopamine, adrenaline and noradrenaline were measured. The results were compared with values obtained during infusion over the same time period of the corresponding volumes of 5% (w/v) d-glucose alone.
3. Energy expenditure calculated from the oxygen consumption and the respiratory exchange ratio was higher than control values during infusion of dopamine (P &lt; 0.001, analysis of variance) specifically at a rate of 10 μg min−1 kg−1 (P &lt; 0.05) when it was 14% higher, but not at a rate 2 of or 5 μg min−1 kg−1. The plasma noradrenaline concentration was 74 and 230% and the blood glucose concentration was 21 and 36% higher than control values at 5 and 10 μg of dopamine min−1 kg−1, respectively (P &lt; 0.01). At 10 μg of dopamine min−1 kg−1 the plasma free fatty acid concentration was 70% and the plasma glycerol concentration was 80% higher than during the control infusion (P &lt; 0.01). The respiratory exchange ratio and the plasma lactate concentration were the same in the two groups and did not alter during the dopamine infusion. The plasma adrenaline concentration rose significantly (P &lt; 0.01), but only transiently, during dopamine infusion at a rate of 2 μg min−1 kg−1.
4. Dopamine at low doses has metabolic effects. It increases the blood glucose concentration and the circulating noradrenaline level at an infusion rate of 5 μg min−1 kg−1. It increases energy expenditure and circulating free fatty acid and glycerol levels at an infusion rate of 10 μg min−1 kg−1, presumably due to stimulation of lipolysis.
A Serial Study of Erythrocyte Sodium Content and Sodium Pump Kinetics in Pregnancy
Authors: MacPhail S. , Thomas T. H. , Wilkinson R. , Davison J. M. , Dunlop W. 
Published: August 2015

1. Normotensive primigravid pregnant women were studied longitudinally during pregnancy and 20 weeks after delivery.
2. Erythrocyte sodium content, ouabain-sensitive sodium flux and sodium pump rate constant were measured in whole blood, and the maximum velocity and sodium affinity of the sodium pump were measured in vitro.
3. Erythrocyte sodium content decreased and the sodium pump rate constant increased up to 26 weeks gestation. The increase in rate constant was due to an increase in the affinity of the sodium pump for sodium up to 20 weeks gestation. After 20 weeks gestation there was an increase in maximum velocity and a decrease in sodium affinity of the sodium pump but no further change in the sodium pump rate constant.
4. At 14 weeks gestation the sodium pump rate constant was correlated with both the maximum velocity and sodium affinity constant. After this time the relationship was much more variable and there was no correlation with the sodium affinity constant. The comparison of measurements of the sodium pump in whole blood and in vitro gave no evidence of sodium pump inhibition.
5. The erythrocyte sodium pump changed throughout gestation with different components to the change, but, overall, available sodium pump activity in blood increased and sodium content decreased.
Tumour Necrosis Factor-α and Endotoxin Induce Less Prostaglandin E2 Production from Hypothalami of Rats Fed Coconut Oil than from Hypothalami of Rats Fed Maize Oil
Authors: Bibby David C. , Grimble Robert F. 
Published: August 2015

1. The primary aim of the study was to determine whether the stimulatory effect of tumour necrosis factor-α and endotoxin on hypothalamic prostaglandin E2 production was influenced by dietary fats containing different amounts of linoleic acid. Rats received diets containing 20% (w/w) maize oil or 19% (w/w) coconut oil plus 1% (w/w) maize oil for 8 weeks.
2. A subsidiary part of the study examined the effect of tumour necrosis factor-α on the ability of the calcium ionophore A23187 to stimulate prostaglandin E2 and leukotriene C4 production by hypothalami from chow-fed rats.
3. While tumour necrosis factor-α enhanced prostaglandin E2 production in response to A23187, neither agent had an effect on leukotriene C4 production.
4. Hypothalami from rats fed maize oil exhibited increased prostaglandin E2 production in response to both pyrogens. This did not occur with hypothalami from rats fed coconut oil.
5. Coconut oil might exert its modulatory effect by bringing about a reduction in membrane phospholipid arachidonic acid content.
Reduced plasma noradrenaline concentrations in simple-obese and diabetic obese patients
Authors: Astrup Arne V. , Christensen Niels Juel , Breum Leif 
Published: August 2015

1. Obesity may be associated with a decreased activity of the sympathetic nervous system and also with a deficiency of the response to stimuli activating the sympathetic nervous system. As insulin activates the sympathetic nervous system, the present study was undertaken to measure the plasma noradrenaline concentration in the fasting state and after 75 g of oral glucose in simple-obese patients (n = 13), in non-insulin-dependent (type 2) diabetic patients (n = 37) and in normal control subjects (n = 12).
2. The fasting plasma noradrenaline concentration was similarly reduced in the simple-obese group and in the diabetic obese group compared with the control group (P = 0.005). The glucose-induced increase in plasma noradrenaline concentration was normal in the simple- obese group, but was abolished in the obese diabetic patients (P = 0.008).
3. Step-wise regression analysis indicated that independent effects on the fasting plasma noradrenaline concentration were exerted by age (r = + 0.32, P = 0.002), glucose concentration (r = −0.32, P = 0.02) and the degree of obesity (r = −0.37, P = 0.007), but not by plasma insulin concentration.
4. These results show that obese patients have a reduced fasting plasma noradrenaline concentration independently of accompanying diabetes, but that the response of noradrenaline to oral glucose is only abolished in the obese diabetic patients.
Serial changes in pulmonary haemodynamics during human pregnancy: a non-invasive study using Doppler echocardiography
Authors: Robson Stephen C. , Hunter Stewart , Boys Richard J. , Dunlop William 
Published: August 2015

1. Serial pulmonary haemodynamic investigations were performed in 13 women before conception, at monthly intervals throughout pregnancy, and then at 6 months after delivery.
2. Mean pulmonary artery pressure was calculated from pulsed Doppler pulmonary velocities. Pulmonary flow was measured by Doppler and cross-sectional echocardiography. These two measurements were used to calculate pulmonary vascular resistance.
3. Mean non-pregnant pulmonary artery pressure was 13.8 mmHg and no significant change was demonstrated during pregnancy.
4. Pulmonary flow increased from 4.88 to 7.19 litres/min during pregnancy.
5. Pulmonary vascular resistance decreased from 2.85 resistance units before pregnancy to 2.17 resistance units at 8 weeks gestation. Thereafter there was no further significant change, values returning to pre-pregnant levels by 6 months after delivery.
Secondary Ischaemia in Rabbit Skin Flaps: The Roles Played by Thromboxane and Free Radicals
Authors: Knight Kenneth R. , Angel Michael F. , Lepore Diana A. , Abbey Paul A. , Arnold Laurence I. , Gray Kathleen A. , Mellow Cary G. , O'Brien Bernard McC. 
Published: August 2015

1. Biochemical mechanisms of ischaemia were investigated in rabbit skin flaps subjected to 2 h of primary ischaemia then, 24 h later, to 4 h of secondary ischaemia. During secondary ischaemia, flaps underwent either total ischaemia (arterial and venous blood supply occluded) or partial ischaemia (vein only occluded). Some of these flaps were treated at the time of reperfusion with the free-radical scavenger superoxide dismutase (EC 1.15.1.1) and/or the thromboxane synthetase inhibitor UK-38,485.
2. After 30 min of reperfusion, superoxide dismutase treatment significantly reduced blood thromboxane levels, elevated during ischaemia. Superoxide dismutase also reduced tissue levels of malonyldialdehyde and xanthine oxidase, indicators of free-radical damage, and restored the depleted tissue levels of superoxide dismutase.
3. UK-38,485 treatment failed to significantly alter any of these tissue free-radical parameters, although this agent significantly reduced blood thromboxane levels.
4. Combined superoxide dismutase plus UK-38,485 treatment was not significantly better than either treatment alone with respect to any parameter.
5. Partial ischaemia led to consistently higher levels of tissue free radicals and blood thromboxane than did total ischaemia. Thus partial ischaemia appears to result in greater free-radical damage than total ischaemia.
6. These results are consistent with the hypothesis that thromboxane acts as a mediator for free-radical damage in the ischaemic changes within the flap.
Stable isotopes in clinical research: safety reaffirmed
Authors: Jones Peter J. H. , Leatherdale Stanley T. 
Published: August 2015

Approaching half a century of stable-isotope usage in human metabolic studies has been without documented significant adverse effect. Side-effects with acute D dosing are transitory with no demonstrated evidence of permanent deleterious action. The threshold of D toxicity has been defined in animals and is far in excess of concentrations conceivably used in human studies. The possibility that D may have additional beneficial pharmacological applications cannot be excluded.
For isotopes other than D, evidence of observed toxicity remains to be produced even at dosages far in excess of the range used in metabolic studies. Absence of adverse effect may be attributable to small mass differences and the similar properties of tracer and predominantly abundant isotope.
Absolute determination of stable isotope toxicity in humans is rendered impossible by ethical considerations. Also, the precision of extrapolating toxicity thresholds from animal studies remains unknown. However, should perturbation of the delicate homoeostatic characteristic of living organisms occur with use of stable isotopes, it is almost undoubtedly at some level of administration greatly in excess of those administered currently in biomedical research.
Clarification of the identity of the major M2 autoantigen in primary biliary cirrhosis
Authors: Fussey Shelley P. M. , West Shauna M. , Lindsay J. Gordon , Ragan C. Ian , James Oliver F. W. , Bassendine Margaret F. , Yeaman Stephen J. 
Published: August 2015

1. In primary biliary cirrhosis, the major M2 autoantigen, reacting with antimitochondrial antibodies in sera from &gt;90% of patients, has been identified as the E2 component of the pyruvate dehydrogenase complex. However, two recent reports suggest that alternative polypeptides may be major autoantigens.
2. The evidence that a 75 kDa subunit of complex I of the respiratory chain is a major autoantigen (Frostell, Mendel-Hartvig, Nelson, Totterman, Bjorkland & Ragan, Scand. J. Immunol. 1988; 28, 157–65) is refuted. The findings of Frostell et al. can be explained by contamination of complex I with the pyruvate dehydrogenase complex, evidence for which is presented here.
3. Inspection of the partial amino acid sequence of an unidentified mitochondrial autoantigen (Muno, Kominami, Ishii, Usui, Saituku, Sakakibara & Namihisa, Hepatology 1990; 11, 16–23) shows that it is the El β-subunit of the pyruvate dehydrogenase complex, previously identified as a major autoantigen, and not a ‘new’ alternative major autoantigen.
4. These findings substantiate previous work showing that the mitochondrial M2 autoantigens identified so far in primary biliary cirrhosis are all polypeptide components of the pyruvate dehydrogenase complex or the other related 2-oxo acid dehydrogenase complexes.
Amino acid metabolism in human subcutaneous adipose tissue in vivo
Authors: Frayn K. N. , Khan K. , Coppack S. W. , Elia M. 
Published: August 2015

1. Arteriovenous differences for alanine, glutamate and glutamine were measured across subcutaneous adipose tissue and forearm muscle in normal subjects.
2. After an overnight fast, adipose tissue showed net production of alanine and glutamine and uptake of glutamate in each of 11 subjects.
3. In seven subjects, adipose tissue blood flow was measured and the measurements were continued for 6 h after eating a mixed meal. The pattern of amino acid metabolism across the adipose tissue was remarkably little disturbed after the meal, except for a short period of apparent uptake of alanine as the concentration of that amino acid rose.
4. The pattern of amino acid metabolism across adipose tissue was qualitatively similar to that across the forearm, although it differed quantitatively in that glutamate uptake was more prominent (compared with glutamine release) in the adipose tissue.
5. The rates of alanine and glutamine release observed suggest that adipose tissue may play a substantial role in the whole-body production of these amino acids.
Intracellular free magnesium in human lymphocytes and the response to lectins
Authors: Ng L. L. , Davies J. E. , Garrido M. C. 
Published: August 2015

1. Intracellular free [Mg2+] was measured in human peripheral blood lymphocytes using a fluorimetric method based on the dye furaptra. It was necessary to correct for the extracellular leakage of the dye by using either 10 mmol/l EDTA or 0.05 mmol/l Mn2+.
2. As the proliferative response of lymphocytes to mitogenic lectins has been linked to a dependence on extracellular Mg2+, the intracellular [Mg2+] was studied in lymphocytes stimulated with various mitogenic and non-mitogenic lectins.
3. Only lymphocytes treated with phytohaemagglutinin-L, a leucoagglutinin from Phaseolus vulgaris that binds to tri- and tetra-antennary complex glycoproteins, showed a marked increase in intracellular [Mg2+]. This effect was partially inhibited by N-acetylgalactosamine. The stimulation by different lectins of the incorporation of [3H]-thymidine into lymphocytes was not correlated to the changes in intracellular [Mg2+].
4. The proliferative response of lymphocytes to lectins is therefore not wholly dependent on a rise in intracellular [Mg2+].
Early loss of neurogenic inflammation in the human diabetic foot
Authors: Walmsley D. , Wiles P. G. 
Published: August 2015

1. Neurogenic inflammation, mediated by nociceptor C fibres, is part of the acute neurovascular response to injury producing the axon reflex flare. Laser Doppler flowmetry was used to measure the flare response induced by the electrophoresis, at various current strengths, of a ring of acetylcholine solution into dorsal foot skin.
2. Nineteen control subjects and 52 long-duration insulin-dependent (Type 1) diabetic patients of similar age (20 without complications; 19 with laser-treated retinopathy; 13 with reduced vibration perception and retinopathy) were studied in order to investigate the possible attenuation of this defence mechanism in diabetes.
3. The maximal (1 mA) flare response [control median (interquartile range): 1.55 (1.16–2.06) arbitrary units] was reduced greatly in neuropathic patients [0.37 (0.24–0.66) arbitrary units; P ≤ 0.001 with respect to all other groups], especially those with a previous history of foot ulceration. The flare was also reduced in some patients with retinopathy alone [1.06 (0.56–1.27) arbitrary units; P &lt; 0.005 with respect to control subjects].
4. No rightward shift of the curve of hyperaemic response plotted against current strength was found, suggesting that the abnormal response was due to axonal loss rather than to dysfunction.
5. Neurogenic inflammation, mediated by small pain fibres, was markedly impaired in a group of diabetic patients at risk of foot ulceration. Furthermore, impairment of this nociceptor C fibre response can develop before clinical large-fibre neuropathy and could itself predispose to foot complications.
Increased blood antioxidant systems of runners in response to training load
Authors: Robertson J. D. , Maughan R. J. , Duthie G. G. , Morrice P. C. 
Published: August 2015

1. Blood antioxidants were measured in venous blood samples from 20 runners and six sedentary individuals. All subjects were male, between 20 and 40 years old, and in steady state with respect to body weight and physical activity patterns. Dietary analysis was undertaken using a 7-day weighed food intake. Correlations were sought between antioxidants in blood and (1) weekly training distance and (2) maximum oxygen uptake. In addition, 12 runners could be classified into two groups undertaking either low (range 16–43 km, n = 6) or high (80–147 km, n = 6) weekly training.
2. Body weight (range 55.3–90.0 kg) and percentage body fat (range 7–19%) both showed negative correlations with the weekly training distance (both P &lt; 0.001). Energy intake and maximum oxygen uptake were both correlated with the weekly training distance (both P &lt; 0.001).
3. Plasma creatine kinase activity, an indicator of muscle damage, was significantly correlated with the weekly training distance (P &lt; 0.01), whereas the plasma concentration of thiobarbituric acid-reactive substances, an indicator of free-radical-mediated lipid peroxidation, decreased with increased maximum oxygen uptake (P &lt; 0.01).
4. Erythrocyte α-tocopherol content was greater in the two running groups (P &lt; 0.05) compared with the sedentary group, and lymphocyte ascorbic acid concentration was significantly elevated in the high-training group (P &lt; 0.01) compared with the low-training group.
5. Erythrocyte activities of the antioxidant enzymes, glutathione peroxidase and catalase, were significantly and positively correlated with the weekly training distance (P &lt; 0.01 and P &lt; 0.05, respectively). Total erythrocyte glutathione content was higher in the two training groups, and was accounted for by an increase in reduced glutathione content.
6. These results indicate that there is an increase in blood antioxidant defence mechanisms associated with endurance training or the related life style, but despite this there is a degree of muscle damage in the training individuals.
Resting energy expenditure in chronic cardiac failure
Authors: Riley M. , Elborn J. S. , McKane W. R. , Bell N. , Stanford C. F. , Nicholls D. P. 
Published: August 2015

1. Resting energy expenditure has previously been shown to be elevated in the acute phase of heart failure, but the situation in the compensated state of chronic cardiac failure is unclear. Resting energy expenditure was assessed in 14 patients with stable chronic cardiac failure and 14 matched control subjects by using indirect calorimetry.
2. Resting energy expenditure was significantly elevated in the patients with chronic cardiac failure (112.6 ± 18.1 versus 87.1 ± 12.2 kJ day−1 kg−1 total body weight, P &lt; 0.0002; mean ± sd) as were resting O2 consumption (3.88 ± 0.64 versus 3.00 ± 0.43 ml min−1 kg−1, P &lt; 0.0002), ventilation (164 ± 40.3 versus 104 ± 16.2 ml min−1 kg−1, P &lt; 0.0001) and heart rate (85.8 ± 16.9 versus 66.6 ± 6.9 beats/min, P &lt; 0.001). Both the resting plasma concentration of noradrenaline (4.48 ± 1.52 versus 2.28 ± 0.96 nmol/l, P &lt; 0.0001) and the serum concentration of free fatty acids (0.78 ± 0.21 versus 0.57 ± 0.27 mmol/l, P &lt; 0.03) were greater in the patients with chronic cardiac failure. Analysis of covariance indicated that most of the difference in resting energy expenditure could be accounted for by the elevated ventilation in the patients with chronic cardiac failure. Arm muscle area, an index of wasting, was lower in the patients with chronic cardiac failure (39.1 ± 13.1 versus 50.5 ± 9.4 cm2, P &lt; 0.02) and resting energy expenditure was found to account for some of this difference.
3. We conclude that an elevated basal metabolism occurs in chronic cardiac failure. It is associated with excess ventilation, and could be an aetiological factor in the development of cardiac cachexia.
Posturally induced microvascular constriction in patients with different stages of leg ischaemia: Effect of local skin heating
Authors: Ubbink Dirk Th. , Jacobs M. J. H. M. , Tangelder G. J. , Slaaf D. W. , Reneman R. S. 
Published: August 2015

1. Skin microcirculation was investigated in 12 asymptomatic subjects and 76 patients, grouped according to their ankle-to-brachial systolic blood pressure index, in order to evaluate to what extent posturally induced microvascular constriction is dependent on the stage of leg ischaemia at different local skin temperatures.
2. Skin microcirculation was assessed in the supine and sitting position by using laser Doppler fluxmetry at unheated skin temperature and at 36°C, and transcutaneous oximetry at 37°C and 44°C.
3. Skin perfusion and oxygenation diminished with decreasing ankle-to-brachial systolic blood pressure index. In healthy control subjects, perfusion and oxygenation were reduced when changing from the supine to the sitting position, but were enhanced in patients with severe leg ischaemia (ankle-to-brachial systolic blood pressure &lt; 30%), indicating disturbed posturally induced vasoconstriction.
4. Increasing the local skin temperature resulted in a higher perfusion and masked the posturally induced vasoconstriction in healthy subjects. In patients with severe leg ischaemia, however, perfusion was unaltered by the temperature increase, apparently because the microvessels were already maximally dilated. The induction of reactive hyperaemia produced no additional increase in perfusion or oxygenation.
5. It is concluded that posturally induced microvascular constriction in the skin is disturbed in patients with severe leg ischaemia (ankle-to-brachial systolic blood pressure index &lt; 30%). Disturbed microvascular constriction upon dependency was also seen in healthy subjects after local skin heating. This suggests that posturally induced vasoconstriction is mainly regulated by local mechanisms.
Haemolytic effects of exercise
Authors: Weight Lindsay M. , Byrne Michael J. , Jacobs Peter 
Published: August 2015

1. Exercise-induced haemolysis has been implicated in the sub-optimal iron status of endurance-trained athletes. Accordingly, erythrocyte survival studies using 51Cr were performed on male and female distance runners (n = 20) and sedentary control subjects (n = 10) in order to determine whether the rate of erythrocyte destruction was altered as a consequence of repetitive exercise training.
2. The chromium half-disappearance time of the male (25.4 ± 3.6 days, mean ± sd) but not the female (28.3 ± 4.6 days) athletes was significantly lower than that of the male (33.1 ± 4.5 days) and female (32.3 ± 2.6 days) control subjects (P &lt; 0.01). The mean erythrocyte lifespan of the male and female distance runners (67.2 ± 22.2 and 72.4 ± 26.0 days, respectively) was significantly shorter than that of the non-exercising male and female subjects (113.4 ± 31.0 and 114.1 ± 29.0 days, respectively) (P &lt; 0.01).
3. There was no correlation between the mean erythrocyte lifespan and the haemoglobin concentration, serum ferritin levels, body mass, weekly training distance, number of years running or daily protein intake. The mean cell volume and reticulocyte count measured in the same athletes before and after completing a standard 42 km marathon race were within the normal range, whereas the plasma haemoglobin levels were elevated (77.0 ± 50.5 mg/l) and the serum haptoglobin levels were decreased (0.89 ± 0.4 g/l) at rest, with a further significant decrease after running (0.69 ± 0.4 g/l) in the latter measurement (P &lt; 0.05).
4. It is concluded that the demonstrated increase in erythrocyte turnover may be sufficient to precipitate an iron deficiency in endurance athletes when dietary intake or absorption does not meet the accelerated erythropoietic demands.