bluuebunny/crossref_metadata_2025 huggingface dataset:
Stress Hormones Given to Healthy Volunteers Alter the Concentration and Configuration of Ribosomes in Skeletal Muscle, Reflecting Changes in Protein Synthesis
Authors: Wernerman Jan , Botta Danielle , Hammarqvist Folke , Thunell Stig , von der Decken Alexandra , Vinnars Erik
Published: August 2015

1. The influence of elevated concentrations of stress hormones on the concentration of ribosomes and the relative proportion of polyribosomes, reflecting protein synthesis in vivo, in human skeletal muscle was investigated. Healthy volunteers were given a 6 h infusion of adrenaline (n = 8), Cortisol (n = 8), a triple-hormone combination of adrenaline, Cortisol and glucagon (n = 8), or saline (n = 8)

2. The total ribosome concentration declined by 30.4 ± 7.2% in the triple-hormone group (P <0.01), by 26.9 ± 8.6% in the Cortisol group (P <0.05) and by 24.8 ± 11.2% in the adrenaline group (P <0.05). The proportion of polyribosomes to total ribosomes decreased by 8.5 ± 2.2% in the triple-hormone group (P <0.05)

3. During hormone infusion the serum glucose levels were enhanced. The insulin concentrations in serum were elevated in the adrenaline group and the triple-hormone group, but not in the Cortisol group. Serum insulin decreased in the control group

4. The results indicate an effect of the combined stress hormone infusion on the total ribosome concentration as well as on the relative abundance of polyribosomes. The single hormones influenced the total ribosome concentration only. The results suggest a critical role for stress hormones in producing the decline in muscle protein synthesis seen after trauma.
Postural vasoconstriction in women during the normal menstrual cycle
Authors: Hassan Ahmad A. K. , Carter G. , Tooke J. E.
Published: August 2015

1. Postural vasoconstriction in the foot was examined in 15 women during the menstrual, follicular and luteal phases of the menstrual cycle, and in 13 age-matched men on two separate occasions, in a constant-temperature environment (22°C).

2. Skin blood flow was measured using laser Doppler flowmetry with the subject lying down, first with the foot maintained at heart level, then with the foot lowered passively 50 cm below the heart. In six of the women, at the time of experiment, serum oestradiol and progesterone were determined by radioimmunoassay. In four women and three men, foot swelling rate was also measured in the dependent foot using a strain gauge plethysmograph in addition to the postural changes in flow. At each visit, in all subjects, arterial blood pressure, heart rate, body temperature, foot skin temperature and body weight were also recorded.

3. The men showed no significant changes in all the variables assessed. In contrast, in women during the luteal phase diastolic and mean arterial pressures were significantly reduced, whereas heart rate, body temperature, foot skin temperature and body weight were significantly increased, as compared with the follicular and menstrual phases of the cycle.

4. During the follicular phase, when oestradiol concentration was high, there were significant reductions in dependent flow and foot swelling rate associated with a significantly augmented postural fall in flow, whereas during the luteal phase, when both oestradiol and progesterone levels were high, there were significant increases in dependent flow and foot swelling rate associated with a significantly impaired postural fall in flow. Four women who reported premenstrual ankle oedema showed significantly higher flow values during the luteal phase than the rest of women.

5. These results confirm the modulating influence of female sex hormones on peripheral blood flow and vascular tone. The partially impaired postural vasoconstrictor response during the luteal phase of the cycle might be partly implicated in the pathogenesis of premenstrual oedema in some women.
Assessment of broadband ultrasound attenuation in the os calcis in vitro
Authors: McCloskey E. V. , Murray S. A. , Charlesworth D. , Miller C. , Fordham J. , Clifford K. , Atkins R. , Kanis J. A.
Published: August 2015

1. We have examined the relationship between the attenuation of broadband ultrasound in the os calcis in vitro and its bone mineral density measured by quantitative computed tomography and by physical density.

2. Broadband ultrasound attenuation was found to correlate closely with physical density (r = 0.85, P < 0.0001), but the correlation was less than that observed between quantitative computed tomography and physical density (r = 0.92, P < 0.0001). Measurements of broadband ultrasound attenuation and quantitative computed tomography were significantly correlated (r = 0.80, P < 0.0001).

3. Partial correlation analysis showed a significant relationship between broadband ultrasound attenuation and bone density, but when the effect of physical density was taken into account no significant correlation was found between broadband ultrasound attenuation and quantitative computed tomography (r = 0.08, not significant).

4. Broadband ultrasound attenuation in three prospective amputees showed a high degree of concordance between measurements in vivo and in vitro, with no interference by surrounding soft tissues.

5. The correlation between physical density and broadband ultrasound attenuation was independent of quantitative computed tomography, suggesting that the technique measures aspects of density which differ from its mineral density. Broadband ultrasound attenuation holds promise as a reproducible, rapid, radiation-free assessment of skeletal status.
Relationship between inspiratory drive and perceived inspiratory effort in normal man
Authors: Clague J. E. , Carter J. , Pearson M. G. , Calverley P. M. A.
Published: August 2015

1. To examine the relationship between the inspiratory effort sensation (IES) and respiratory drive as reflected by mouth occlusion pressure (P0.1) we have studied loaded and unloaded ventilatory responses to CO2 in 12 normal subjects.

2. The individual coefficient of variation of the effort sensation response to CO2 (IES/Pco2) between replicate studies was 21% and was similar to the variability of the ventilatory response (VE/Pco2) (18%) and the occlusion pressure response (P0.1/Pco2) (22%).

3. IES was well correlated with P0.1 (r >0.9) for both free-breathing and loaded runs.

4. Resistive loading reduced the ventilatory response to hypercapnia from 19.3 1 min−1 kPa−1 (sd 7.5) to 12.6 1 min−1 kPa−1 (sd 3.9) (P <0.01). IES and P0.1 responses increased with resistive loading from 2.28 (sd 0.9) to 3.15 (sd 1.1) units/kPa and 2.8 (sd 1.2) to 3.73 (sd 1.5) cmH2O/kPa, respectively (P <0.01).

5. Experimentally induced changes in Pco2 and respiratory impedance were accompanied by increases in IES and P0.1. We found no evidence that CO2 increased IES independently of its effect on respiratory drive.
Tissue zinc status and drug elimination in patients with chronic liver disease
Authors: Barry Michael , Keeling P. W. N. , Feely John
Published: August 2015

1. The zinc status and drug-metabolizing ability of 15 patients with histologically diagnosed hepatic cirrhosis were studied. Zinc status was assessed using both serum and leucocyte zinc concentrations, and drug-metabolizing ability was assessed by antipyrine kinetics.

2. Patients with cirrhosis were found to have lower serum and leucocyte zinc concentrations when compared with a healthy control group.

3. Leucocyte zinc content and antipyrine clearance were correlated. Those patients with the lowest leucocyte zinc content had the greatest impairment of drug metabolism. Antipyrine elimination and serum zinc concentrations were not correlated.

4. Leucocyte zinc concentrations and antipyrine clearance were not influenced by the severity of liver dysfunction, as assessed by using the Child Turcotte classification.

5. These results suggest that tissue zinc depletion in some patients with hepatic cirrhosis may explain in part the impaired capacity to metabolize drugs.
Microheterogeneity of α1-antichymotrypsin in the management of giant-cell arteritis and polymyalgia rheumatica
Authors: Hachulla Eric , Laine Anne , Hayem Annette
Published: August 2015

1. Using crossed immunoaffinity electrophoresis with free concanavalin A in the first dimension, we studied the glycan microheterogeneity of α1-antichymotrypsin in sera from patients with giant-cell arteritis and/or polymyalgia rheumatica, and its variation in the serum of several of these patients during induction of disease remission by prednisone therapy and possible further recurrence of giant-cell arteritis and/or polymyalgia rheumatica.

2. In the serum of patients with active disease we observed increased proportions of concanavalin A non-reactive and concanavalin A weakly reactive fractions. The results were expressed as the ratio of concanavalin A non-reactive fraction plus concanavalin A weakly reactive fraction to concanavalin A reactive fraction, called Rα1-ACT. An Rα1-ACT higher than 1.8 (upper normal value) was found in 30/31 sera from patients with active disease (sensitivity 97%) and in 2/22 sera from patients with inactive disease (specificity 91%).

3. The erythrocyte sedimentation rate and the serum C-reactive protein level, common markers of biological inflammation, are usually elevated in active giant-cell arteritis and/or polymyalgia rheumatica. The two parameters are commonly used to guide the therapy during the course of the disease, but they have no specificity. An erythrocyte sedimentation rate of greater than 30 mm/h was found in 30/31 sera from patients with active disease (sensitivity 97%) and in 5/22 sera from patients with inactive disease (specificity 77%). Our results show that α1-antichymotrypsin microheterogeneity provides a precise marker of giant-cell arteritis and/or polymyalgia rheumatica activity, particularly when the serum C-reactive protein level is normal or when the erythrocyte sedimentation rate is still high in treated patients. We found a better positive prediction value for Rα1-ACT than for erythrocyte sedimentation rate (94% and 86%, respectively). By determining the Rα1-ACT it is thus possible to follow the exacerbation of the disease when the dose of prednisone is tapered.

4. The correlation coefficients between clinical symptoms, erythrocyte sedimentation rate, levels of C-reactive protein or α1-antichymotrypsin, and Rα1-ACT values were determined. The highest correlation occurred between Rα1-ACT and erythrocyte sedimentation rate (r = 0.57, P <0.0001).

5. Three case reports illustrated the value of determining Rα1-ACT as a useful adjunct test for the diagnosis of giant-cell arteritis and/or polymyalgia rheumatica.
Renal functional reserve in patients with essential hypertension: Effect of inhibition of the renin-angiotensin system
Authors: Valvo Enrico , Casagrande Patrizia , Bedogna Valeria , Dal Santo Francesca , Alberti Daniele , Fontanarosa Cristina , Braggio Paolo , Maschio Giuseppe
Published: August 2015

1. Urinary albumin excretion and the effect of an acute oral protein load (a meat meal) on glomerular filtration rate ('renal functional reserve') were evaluated in 15 essential hypertensive patients with preserved renal function and compared with 12 normal subjects.

2. Seven patients had microalbuminuria (>30 mg/day) that was not correlated with blood pressure values.

3. After an oral protein load, an average increase of 20% in glomerular filtration rate (from 91 ± 19 to 110 ± 27 ml min−1 1.73 m−2) was found in the hypertensive patients. This change was not statistically different from that observed in normal controls (from 102 ± 7 to 124 ± 9 ml min−1 1.73 m−2). The glomerular response in hypertensive patients was independent of age, duration of hypertension, blood pressure, plasma renin activity, urinary albumin excretion and retinal vascular alterations.

4. All patients were re-evaluated after 6 weeks treatment with a new orally active angiotensin-converting enzyme inhibitor, benazepril. Systolic, diastolic and mean blood pressures were lowered in all the patients, but the drug did not affect the glomerular response to acute protein ingestion or the magnitude of urinary albumin excretion.

5. The findings of a normal ‘renal functional reserve’ and a lack of change in both urinary albumin excretion and the glomerular response after angiotensin-converting enzyme inhibition cast doubt on the existence of increased intraglomerular pressure in hypertensive patients.
Skeletal muscle and whole-body protein turnover in cirrhosis
Authors: Morrison W. L. , Bouchier I. A. D. , Gibson J. N. A. , Rennie M. J.
Published: August 2015

1. We investigated arteriovenous exchanges of tyrosine and 3-methylhistidine across leg tissue in the postabsorptive state as specific indices of net protein balance and myofibrillar protein breakdown, respectively, in eight patients with cirrhosis and in 11 healthy control subjects. Whole-body protein turnover was also measured using l-[1-13C]leucine.

2. Leg efflux of tyrosine was 45% greater in cirrhotic patients than in normal control subjects [−6.5(1.4 to −19.1) vs −4.2 (−2.2 to −7.7) μmol min−1 100 mg−1 of leg, median (range), P <0.025]. 3-Methylhistidine efflux was not significantly altered.

3. In cirrhosis, whole-body leucine flux was normal but whole-body leucine oxidation was elevated so that whole-body protein synthesis was depressed by 17%.

4. The results indicate the predominant mechanism of muscle wasting in cirrhosis to be a fall in muscle protein synthesis, which is accompanied by an overall fall in whole-body protein turnover.
Cutaneous Vascular Responses Evoked in the Hand by the Cold Pressor Test and by Mental Arithmetic
Authors: Marriott I. , Marshall Janice M. , Johns E. J.
Published: August 2015

1. Laser Doppler flowmetry has been used to study changes in cutaneous erythrocyte flux produced in the hand (i) on successive immersion of the contralateral hand in water at 20°C (cold test) and then in water at 0–4°C (cold pressor test), and (ii) by mental arithmetic.

2. In 11 subjects, placing the right hand in water at 20°C for 2 min induced a significant decrease in cutaneous erythrocyte flux in the contralateral hand and a significant fall in mean arterial pressure. Cutaneous vascular resistance, calculated as arterial pressure/cutaneous erythrocyte flux, showed no significant change. Thus, the decrease in erythrocyte flux was apparently due to a fall in perfusion pressure.

3. Subsequent immersion of the right hand in water at 0–4°C for 2 min caused a significant decrease in erythrocyte flux in the contralateral hand and a significant rise in mean arterial pressure. It is concluded that the cold pressor response evoked from one hand elicited a substantial reflex vasoconstriction in the skin of the other hand; accordingly, calculated cutaneous vascular resistance increased significantly.

4. Eight subjects performed mental arithmetic for two periods of 2 min separated by a rest period of 2 min. By the end of the second minute of each period of mental arithmetic there was a significant decrease in erythrocyte flux. Mean arterial pressure increased significantly in the first period only, but calculated cutaneous vascular resistance increased in both periods, consistent with cutaneous vasoconstriction.

5. The cold pressor test and mental arithmetic are aversive stimuli that evoke the characteristic pattern of the alerting or defence response which includes splanchnic vasoconstriction and muscle vasodilatation. Previous studies on the cutaneous vascular component of this response have yielded equivocal results. The present study provides firm evidence that it includes cutaneous vasoconstriction, at least in the hand.
Effect of Atrial Natriuretic Factor on Bronchomotor Tone in the Normal Human Airway
Authors: Hulks G. , Jardine A. G. , Connell J. M. C. , Thomson N. C.
Published: August 2015

1. Asthmatic patients bronchodilate in response to infused atrial natriuretic factor. We wished to determine whether the airways of normal subjects responded in a similar way.

2. Changes in airway resistance, as determined by specific airway conductance, were measured in eight normal subjects in response to intravenous infusion of atrial natriuretic factor at doses of 0.5, 2 and 10 pmol rnin−1 kg−1.

3. No significant effect was observed on specific airway conductance at any rate of infusion despite maximum mean (sem) plasma levels of 597 (62) pg of atrial natriuretic factor/ml in peripheral venous blood.

4. A second study was performed using six of the eight original subjects and employing a pharmacological dose of 50 pmol of atrial natriuretic factor min−1 kg−1. This produced mean plasma levels of 2056 pg/ml and a mean increase of 31% in specific airway conductance.

5. It is concluded that pharmacological, but not pathophysiological, elevations of plasma atrial natriuretic factor may significantly alter bronchomotor tone in normal subjects.
Orthostatic Circulatory Control in the Elderly Evaluated by Non-Invasive Continuous Blood Pressure Measurement
Authors: Imholz B. P. M. , Dambrink J. H. A. , Karemaker J. M. , Wieling W.
Published: August 2015

1. Continuous orthostatic responses of blood pressure and heart rate were measured in 40 healthy and active elderly subjects over 70 years of age in order to assess the time course and rapidity of orthostatic cardiovascular adaptation in old age.

2. During the first 30 s (initial phase) the effects of active standing and passive head-up tilt closely resembled those observed earlier in younger age groups. Standing up was accompanied by a drop (mean ± SD) in systolic and diastolic blood pressures of 26 ± 13 mmHg and 12 ± 18 mmHg, respectively, at around 10 s, and a subsequent rise up to 11 ± 17 mmHg and 8 ± 6 mmHg above supine values at around 20 s. The drop in blood pressure upon standing was accompanied by a transient increase in heart rate with a maximum of 13 beats/min, followed by a gradual decrease to 7 beats/min above supine levels. These characteristic transient changes were absent upon a passive head-up tilt.

3. After 1–2 min of standing (early steady-state phase) diastolic blood pressure and heart rate increased significantly after active and passive postural changes. On average, for all subjects systolic blood pressure tended to increase from control during 5–10 min standing, reaching a significant difference at 10 min. During standing, the largest increases in systolic blood pressure were found in subjects with the lowest supine blood pressures.

4. In conclusion, for the investigation of orthostatic circulatory responses in elderly subjects the following factors have to be taken into account: active versus passive changes in posture, the timing of the blood pressure reading, and the level of supine blood pressure.
Effects of Lead and a Low-Molecular-Weight Endogenous Plasma Inhibitor on the Kinetics of Sodium—Potassium-Activated Adenosine Triphosphatase and Potassium-Activated p-Nitrophenylphosphatase
Authors: Weiler Elmar , Khalil-Manesh Farhad , Gonick Harvey C.
Published: August 2015

1. Lead, ouabain and an endogenous plasma inhibitor were all found to be potent inhibitors of purified hog cerebral cortex sodium—potassium-activated adenosine triphosphatase and potassium-stimulated p-nitrophenylphosphatase.

2. The kinetic characteristics of inhibition of both enzymes by lead and the endogenous plasma inhibitor differed in several respects. For sodium—potassium-activated adenosine triphosphatase, lead and the endogenous plasma inhibitor were non-competitive inhibitors with respect to potassium; lead was competitive with respect to sodium, whereas the endogenous plasma inhibitor had no effect; lead was competitive with respect to magnesium adenosine triphosphate, whereas the endogenous plasma inhibitor was uncompetitive. For potassium-activated p-nitrophenylphosphatase, both lead and the endogenous plasma inhibitor were competitive with respect to potassium; lead showed a mixed type of inhibition with respect to p-nitrophenylphosphate, whereas the endogenous plasma inhibitor was non-competitive.

3. Lead and the endogenous plasma inhibitor exhibited synergistic inhibitory activity on sodium—potassium-activated adenosine triphosphatase.

4. These results suggest that lead could play a contributory role in the pathogenesis of essential hypertension via an additive inhibition of vascular smooth muscle sodium—potassium-activated adenosine triphosphatase.
Effect of Endothelin on the Function of the Isolated Perfused Working Rat Heart
Authors: Firth J. D. , Roberts A. F. C. , Raine A. E. G.
Published: August 2015

1. The effect of endothelin on the performance of the isolated perfused working rat heart has been examined.

2. A low concentration of endothelin (60 pmol/l) produced a gradual but sustained increase in cardiac output; coronary vascular resistance was unaffected.

3. A high concentration of endothelin (600 pmol/l) produced a rapid increase in cardiac output, followed by a marked fall in cardiac output as progressive, severe coronary vasoconstriction developed.

4. The coronary vasoconstriction induced by endothelin (600 pmol/l) was partially blocked by nicardipine (0.5 pmol/l)

5. In the presence of either nicardipine (0.5 μmol/l) or verapamil (0.2 μmol/l), the increment in cardiac output induced by endothelin (600 pmol/l) was greater than that induced by the addition of the same concentration of endothelin to hearts which had not been exposed to calcium-entry blockers.

6. The effect of endothelin on myocardial contractility has a different time course, concentration dependence and response to calcium-entry blockade than the effect on the coronary vasculature. This suggests that different mechanisms are involved in the generation of the myocardial and vascular responses to endothelin.
Metabolism of 15N-Labelled Urea in the Functioning and Defunctioned Human Colon
Authors: Moran B. J. , Jackson A. A.
Published: August 2015

1. The luminal metabolism of urea was studied using double-labelled urea ([15N2]urea) which was placed in the lumen of the colon through a colostomy. The recovery of label was measured as [15N2]urea or [14N,15N]urea in urine and as 15N in stool.

2. Five patients with a loop colostomy allowed a comparison of the right functioning colon with the left defunctioned colon in the same individual. Five subjects with a left end-colostomy enabled a comparison of the right with the left functioning colon.

3. A significantly greater proportion of labelled urea was recovered as [15N2]urea in the urine when the dose was placed in the left defunctioned colon (29%) compared with either the left or the right functioning colon (9 and 4%, respectively). This is interpreted as being a result of a decrease in the bacterial activity and concomitant urea hydrolysis in the defunctioned colon.

4. On average more than half of the label was retained in the body, regardless of whether the urea was placed in the functioning or the defunctioned colon, on the left or on the right.

5. The data confirm that the colon is permeable to the intact urea molecule. Intraluminal urea is readily hydrolysed in the functioning colon. A large proportion of the nitrogen released by urea hydrolysis may be retained within the metabolic nitrogen pool of the host. There are significant differences in the handling of urea nitrogen in the defunctioned colon relative to the functioning colon.
Effect of Amiodarone on erythrocyte Shape and Membrane Properties
Authors: Reinhart W. H. , Rohner F.
Published: August 2015

1. Amiodarone is a potent anti-arrhythmic drug with lipophilic properties. The intercalation of such a drug into the membrane of erythrocytes may alter their shape and have an impact on the flow properties of blood. We therefore studied the influence of amiodarone on erythrocyte shape and deformability in vitro and in vivo.

2. Incubation in vitro with increasing amiodarone concentrations led to a progressive stomatocytic shape transformation and a decreased deformability of the erythrocytes.

3. Amiodarone treatment in eight patients did not affect erythrocyte morphology and deformability. However, an increase in the membrane cholesterol/phospholipid ratio was found.

4. The stomatocytic shape transformation of erythrocytes in vitro indicates that amiodarone intercalates in the inner hemileaflet of the lipid bilayer leading to membrane internalization. These results shed light on the interaction of amiodarone with biomembranes.
Platelet Angiotensin II Binding and Plasma Renin Concentration, Plasma Renin Substrate and Plasma Angiotensin II in Human Pregnancy
Authors: Baker Philip N. , Pipkin Fiona Broughton , Symonds E. Malcolm
Published: August 2015

1. The results are presented of a cross-sectional study of 25 non-pregnant and 125 pregnant/postnatal women in whom platelet angiotensin II binding and plasma angiotensin II, plasma renin concentration and plasma renin substrate were measured.

2. Platelet angiotensin II binding was significantly lower in the first-trimester patients as compared with the non-pregnant women (P < 0.001). Specific binding remained low in the second and third trimesters, and in those patients studied 24 h after delivery. However, higher values, approximating to the non-pregnant level, were found 6 weeks postnatally (n = 25 for each group).

3. Plasma angiotensin II, plasma renin concentration and plasma renin substrate increased in pregnancy, with the increase becoming statistically significant as compared with the non-pregnant women in the second trimester. Maximal median values of plasma angiotensin II and plasma renin substrate were found in the third trimester, but maximal median values of plasma renin concentration were found in the second trimester. The concentrations of all three hormones fell after delivery.

4. There was an inverse correlation between platelet angiotensin II binding and simultaneously measured endogenous levels of plasma angiotensin II (P < 0.02) and plasma renin substrate (P < 0.05) in the 25 non-pregnant subjects. These findings support the concept of the angiotensin II receptor concentration being regulated by the plasma angiotensin II level. There was no correlation between platelet angiotensin II binding and plasma renin concentration.

5. In pregnancy, no correlation between platelet angiotensin II binding and plasma angiotensin II, plasma renin concentration or plasma renin substrate was found. This suggests that any regulation by plasma angiotensin II may not operate in pregnancy, when reduced binding concentrations are present. No statistically significant correlation was found at either 24 h or 6 weeks after delivery.
Metabolic Regulation of Renal Gluconeogenesis in Response to Sepsis in the Rat
Authors: Salleh M. , Ardawi M. , Khoja Samir M. , Newsholme Eric A.
Published: August 2015

1. The regulation of renal gluconeogenesis was studied in rats made septic by a caecal ligation and puncture technique.

2. Blood glucose concentrations were not markedly different in septic rats, but lactate, pyruvate and alanine concentrations were markedly increased, compared with sham-operated rats. Conversely, blood ketone body concentrations were significantly decreased in septic rats. Both plasma insulin and glucagon concentrations were markedly elevated in response to sepsis.

3. The maximal activities of glucose-6-phosphatase (EC 3.1.3.9), fructose-1,6-bisphosphatase (EC 3.1.3.11), pyruvate carboxylase (EC 6.4.1.1) and phosphoenol-pyruvate carboxykinase (EC 4.1.1.49) were markedly decreased in kidneys obtained from septic rats, suggesting diminished renal gluconeogenesis.

4. Renal concentrations of lactate, pyruvate and other gluconeogenetic intermediates were markedly elevated in septic rats, whereas those of acetyl-CoA and fructose 2,6-bisphosphate were decreased and unchanged, respectively.

5. The rate of gluconeogenesis from added lactate, pyruvate and glycerol was decreased in isolated incubated renal tubules from septic rats.

6. Sepsis decreased the arteriovenous concentration difference for glucose, lactate, and alanine. Septic rats showed decreased net rates of glucose production and net rates of removal of lactate and alanine as compared with sham-operated controls.

7. It is concluded that the diminished capacity for renal gluconeogenesis in septic rats could be the result of changes in the maximal activities or regulation of key non-equilibrium gluconeogenic enzymes or both, but the effect of other factors (e.g. toxins) has not been excluded.
Evidence for Abnormal Na+/H+ Antiport Activity Detected by Phosphorus Nuclear Magnetic Resonance Spectroscopy in Exercising Skeletal Muscle of Patients with Essential Hypertension
Authors: Dudley C. R. K. , Taylor D. J. , Ng L. L. , Kemp G. J. , Ratcliffe P. J. , Radda G. K. , Ledingham J. G. G.
Published: August 2015

1. Exercise-induced pH changes in skeletal muscle were studied in a group of eight subjects with essential hypertension by using 31P n.m.r. spectroscopy.

2. Leucocyte Na+/H+ antiport activity was measured in vitro in the same subjects using a pH-sensitive fluorescent dye.

3. Resting skeletal muscle pH and unstimulated leucocyte pH values were similar to those in control subjects, but increased Na+/H+ antiport activity was demonstrated in the leucocytes from hypertensive subjects by acid loading in vitro. Decreased skeletal muscle acidification and an increased rate of pH recovery was also demonstrated in vivo in these same patients during an acid load induced by isotonic exercise.

4. These findings suggest that the increased cellular Na+/H+ antiport activity, which has been demonstrated in vitro in essential hypertension, also affects the biochemical response of skeletal muscle to physiological levels of exercise. This strengthens the argument that increased Na+/H+ antiport activity in hypertension is a generalized and physiologically relevant cellular abnormality.
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 < 0.001, analysis of variance) specifically at a rate of 10 μg min−1 kg−1 (P < 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 < 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 < 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 < 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 >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 < 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 < 0.001). Energy intake and maximum oxygen uptake were both correlated with the weekly training distance (both P < 0.001).

3. Plasma creatine kinase activity, an indicator of muscle damage, was significantly correlated with the weekly training distance (P < 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 < 0.01).

4. Erythrocyte α-tocopherol content was greater in the two running groups (P < 0.05) compared with the sedentary group, and lymphocyte ascorbic acid concentration was significantly elevated in the high-training group (P < 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 < 0.01 and P < 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.