bluuebunny/crossref_metadata_2025 huggingface dataset:
Effects of heroin addiction on the responses of glucose, C-peptide and insulin to a standard meal
Authors: Zandomeneghi R. , Luciani A. , Massari M. , Montanari P. , Pavesi C.
Published: August 2015

1. The aim of the study was to examine the responses of plasma glucose, C-peptide immunoreactivity (CPR) and total immunoreactive insulin (IRI) to a standard meal in heroin addicts, since the presence of immunoreactive β-endorphin has been demonstrated in human endocrine pancreas.

2. Ten heroin addicts and 10 control subjects participated in the study. The addicts had been taking heroin (from 0.5 to 2 g/day) for at least 2 months and they had no detectable diseases.

3. After a 12 h fast, each subject received a standard meal; blood samples were taken at − 15, 0, 15, 30, 60 and 120 min to determine glucose, CPR and IRI. Calculation of the CPR/IRI molar ratio was used as a semiquantitative estimation of the hepatic extraction of insulin.

4. No difference in plasma glucose was observed between the groups. Addicts had lower CPR than normals at 15, 30 and 120 min (P < 0.01). On the contrary, IRI was higher in addicts than in normals (P < 0.05 at − 15 and 0 min, P < 0.01 at 15, 30 and 60 min), except at 120 min. The CPR/IRI molar ratio was lower in addicts (P < 0.01).

5. Heroin addiction seems to produce a β-cell failure and contemporaneously a state of hyperinsulinaemia; blood glucose remains in the normal range.

6. We conclude that chronic heroin addiction may produce a change in the rate of hepatic extraction of insulin.
Effects of a specific antidiuretic agonist on cardiac output and its distribution in intact and anephric dogs
Authors: Liard Jean-Francois
Published: August 2015

1. The specific antidiuretic agonist [4-valine, 8-d-arginine]vasopressin (VDAVP) was administered intravenously to seven conscious dogs at a rate of 10 ng min−1 kg−1. Cardiac output (aortic electromagnetic flowmeter), mean arterial pressure and regional blood flows (radioactive microspheres) were measured before and after 30 min of infusion.

2. Mean arterial pressure fell from 89.9 ± 4.5 (mean ± sem) to 82.3 ± 5.9 mmHg and cardiac output increased from 115.4 ± 8.7 to 163.0 ± 14.4 ml min−1 kg−1. Total peripheral resistance decreased from 41.6 ± 3.7 to 27.8 ± 3.6 units and heart rate increased from 79.2 ± 5.9 to 123.2 ± 5.9 beats/min. Blood flow increased significantly in the myocardium, fat and skeletal muscle vascular bed.

3. In another group of six dogs subjected to a similar protocol 24 h after bilateral nephrectomy, mean arterial pressure fell from 102.2 ± 5.3 to 82.7 ± 3.4 mmHg and cardiac output increased from 125.6 ± 3.0 to 171.2 ± 4.0 ml min−1 kg−1. Total peripheral resistance decreased from 39.3 ± 3.4 to 23.4 ± 1.3 units and heart rate increased from 84 ± 4.9 to 113.3 ± 4.3 beats/min. The increase in cardiac output and the fall in total peripheral resistance did not differ significantly between intact and anephric dogs. Regional blood flow responses differed in some respects in the two groups studied, but there was no evidence that the vasodilatory action of VDAVP depended on the presence of the kidneys.

4. These results indicate that the vasodilatation elicited by the antidiuretic agonist VDAVP in intact dogs is limited to a few vascular beds. Furthermore, this vasodilatation appears to be independent from the renal V2-vasopressin receptors.
Relative efficacy of oral verapamil and digoxin alone and in combination for the treatment of patients with chronic atrial fibrillation
Authors: Pomfret S. M. , Beasley C. R. W. , Challenor V. , Holgate S. T.
Published: August 2015

1. The efficacy of verapamil alone, or in combination with digoxin, was compared with digoxin alone in eight patients with chronic atrial fibrillation in this double-blind placebo-controlled study.

2. After 2 weeks on each treatment regimen, heart rate at rest and during progressive load treadmill exercise, left ventricular function at rest and nocturnal heart rate were measured.

3. Oral verapamil alone at a dose of 80 mg three times daily, or 40 mg of verapamil three times daily in combination with 0.25 mg of digoxin daily, was superior to digoxin alone in doses associated with high serum digoxin concentrations (mean ± sem 1.6 ± 0.3 μg/l). This superiority manifested as greater control of heart rate during work rates equivalent to regular daily activities, and was not associated with deterioration in left ventricular function or worsening nocturnal bradycardia.

4. We conclude that the treatment of choice in patients with chronic atrial fibrillation is either 80 mg of verapamil three times daily or 40 mg of verapamil three times daily in combination with digoxin.
A randomized controlled trial of the effect on blood pressure of dietary non-meat protein versus meat protein in normotensive omnivores
Authors: Prescott Susan L. , Jenner David A. , Beilin Lawrence J. , Margetts Barrie M. , Vandongen Robert
Published: August 2015

1. A randomized, controlled trial was carried out to examine whether changes in type and amount of dietary protein were responsible for earlier observations of blood-pressure-lowering effects of lacto-ovo-vegetarian diets.

2. Sixty-four subjects were pair-matched for sex, age, weight and sitting systolic blood pressure, and were randomly allocated to receive one of two types of protein supplement: one containing proteins from meat, the other proteins from non-meat sources. The supplements were balanced in terms of other nutrients. Consumption of other meat, poultry or fish was prohibited.

3. Sitting and standing blood pressures, weight, dietary intakes and plasma and urinary electrolytes were measured at regular intervals during the 12 weeks of trial. Urinary 3-methylhistidine was used as a measure of compliance.

4. Fifty subjects completed the trial. There were no statistically significant blood pressure differences between groups either at baseline or at end-of-trial, neither were there any substantive differences in mean blood pressure changes between baseline and end-of-trial. 3-Methylhistidine excretion was significantly lower in subjects on the non-meat diet.

5. The results suggest that the protein components of the lacto-ovo-vegetarian diet are not responsible for the blood-pressure-lowering effects of that diet.
Failure of impedance plethysmography to follow exercise-induced changes in limb blood flow
Authors: Hughson Richard L.
Published: August 2015

1. The blood flow in the forearm and the calf of six healthy volunteers was measured at rest and after exercise by impedance plethysmography using pulsatile (QZp) and venous occlusion (QZocc) methods, and by venous occlusion strain gauge plethysmography (Qsg).

2. At rest, the impedance QZp method gave values slightly higher than those of Qsg. In the forearm, the ratio QZp to Qsg was 1.26 in the supine position and 1.97 in the upright sitting position. For the calf muscle, the ratios were 1.08 in the supine position and 1.23 in the upright position.

3. Immediately after exercise, Qsg increased from resting values of approximately 2–4 ml min−1 100 ml−1 to mean values of 16–25 ml min−1 100 ml−1 in upright and supine arm or leg exercise. In contrast, the QZp values after exercise increased to only 3.1–4.6 ml min−1 100 ml−1. QZocc likewise failed to show increases in flow except in the supine leg exercise, where flow increased to 8.7 ml min−1 100 ml−1.

4. In an additional subject, it was shown that electrode position had no significant effect on the QZp blood flow measurement after exercise.

5. The failure of QZp to accurately follow the change in Qsg with exercise was probably due in part to pulsatile venous outflow. In addition, changes in microvessel packed cell volume and shear rate may influence the observed QZp. It is concluded that impedance plethysmography is not valid for estimation of limb blood flow during reactive hyperaemia after exercise.
Rates of muscle protein synthesis in paraspinal muscles: Lateral disparity in children with idiopathic scoliosis
Authors: Gibson J. N. A. , McMaster M. J. , Scrimgeour C. M. , Stoward P. J. , Rennie M. J.
Published: August 2015

1. The rate of paraspinal (multifidus) muscle protein synthesis was measured bilaterally at the top, apex and bottom of the thoracic curve in nine children with an idiopathic scoliosis, using the stable-isotope-labelled amino acid l-[1-13C]leucine.

2. No significant difference was observed in rates of muscle protein synthesis between the two sides of the spine, at the levels of the first vertebrae in neutral alignment at the top and bottom of the curve. However, in every patient, at the apex of the spinal curve, synthesis was higher on the convexity than on the concavity (0.077 ±0.04 %/h convex, 0.052 ±0.02 %/h concave, means ±sd, P < 0.01).

3. Muscle RNA activity (μg of protein synthesized h−1 μg−1 of RNA) was lower at the curve apices on the concave than the convex side (0.019 ± 0.09 μg h−1 μg−1 convex apex, 0.016 ±0.06 μg h−1 μg−1 concave apex, P < 0.05). Activities were similar on the two sides at the top and bottom of the curve.

4. Differences in muscle histology between the two sides were also observed only at the apex, with a lower type I fibre diameter (50.9 ±8.5 μm convex, 38.3 ±2.4 μm concave, P < 0.05) and a lesser proportion of type I fibres (63 ± 12% convex, 49 ±9% concave, P < 0.05) on the concavity.

5. The results are consistent with effects on muscle protein turnover secondary to an increased muscle contractile activity on the curve convexity and functional immobilization of the muscle on the curve concavity.
Fluoride therapy in osteoporosis: Acute effects on parathyroid and mineral homoeostasis
Authors: Stamp Trevor C. B. , Jenkins Michael V. , Loveridge Nigel , Saphier Peter W. , Katakity Monica , MacArthur Sarah E.
Published: August 2015

1. Acute metabolic effects of sodium fluoride therapy were analysed among 41 osteoporotic patients already receiving large calcium supplements, 33 of whom underwent simultaneous metabolic balance studies.

2. Mean serum calcium fell transiently within 24–48 h by 0.03 ±0.07 (sd) mmol/l (P < 0.01) and phosphorus by 0.06±0.08 (sd) mmol/l (P < 0.001). In a subgroup, ionized calcium fell and biologically active parathyroid hormone (bio-PTH) rose more than fivefold (P < 0.01). Urine calcium rose after an insignificant fall.

3. Pretreatment calcium and phosphorus balances were significantly positive and did not change overall during the first 8 days of treatment. However, on analysing balances in two groups relative to serum changes, in patients whose serum levels changed least sodium fluoride increased faecal calcium (P < 0.025) and phosphorus (P < 0.01) and reduced calcium balance (P < 0.01), giving a mean balance difference between the two groups of 2.1 mmol daily (P < 0.001).

4. Very small changes in serum levels therefore indicate well-marked metabolic responses: sodium fluoride acutely stimulates bio-PTH activity and must also enhance mineral uptake from circulation into tissue(s). By separate and opposing action(s) it inhibits intestinal calcium and phosphorus absorption, predominantly in those whose serum levels remain stable. All these effects may be relevant to long-term therapeutic results.
Atrial natriuretic peptide and adaptation of sodium urinary excretion in patients with chronic renal failure
Authors: Czekalski Stanislas , Michel Catherine , Dussaule Jean-Claude , Touraine Philippe , Mignon Francoise , Ardaillou Raymond
Published: August 2015

1. In order to examine the potential role of endogenous atrial natriuretic peptide (ANP) in modulating the increased sodium excretion per nephron in chronic renal failure, we studied healthy subjects with normal renal function (group I) and patients with moderate (group II) or severe chronic renal failure (group III) before, during and after administration of an intravenous sodium load. All subjects had been on a controlled diet containing 120 mmol of sodium per day for 5 days before the study.

2. Under basal conditions, plasma ANP and fractional excretion of sodium (FENa) were highest in group III. Both parameters increased in response to the sodium load in the three groups studied (P < 0.001). Changes with time differed from group to group (P < 0.05), the more marked response for both parameters being observed in group III. After adjustment with respect to plasma ANP (analysis of covariance), FENa was no longer modified in response to the sodium load, whereas adjustment of FENa with respect to mean blood pressure was without consequence on the significance of its change with time. This demonstrates that plasma ANP, but not mean blood pressure, represents the main factor producing variation in FENa during and after the sodium load.

3. These results suggest an important role for plasma ANP in promoting adaptation of short-term sodium excretion in response to an acute sodium load in patients with chronic renal failure who ingest a normal sodium intake.
Effects of the somatostatin analogue SMS 201–995 (sandostatin) on mouth-to-caecum transit time and absorption of fat and carbohydrates in normal man
Authors: MøLler Niels , Petrany Guyla , Cassidy David , Sheldon William L. , Johnston Desmond G. , Laker Michael F.
Published: August 2015

1. Somatostatin analogues, such as SMS 201–995 (sandostatin), have been suggested as treatment for a variety of disease states including acromegaly, secretory gastrointestinal tumours and diabetes mellitus.

2. Somatostatin-14 has actions to prolong gastrointestinal transit time and inhibit intestinal absorption, and we have therefore studied the effects of SMS 201–995 on these processes. Five male subjects received a test meal having been given either saline or 50 μg of SMS 201–995 subcutaneously 30 min before ingestion.

3. SMS 201–995 caused a delay in mouth-to-caecum transit time for lactulose assessed by breath hydrogen analysis (316 ± 17 vs 192 ± 14 min, mean ±sem, P < 0.01), a delay (234 vs 120 min, P < 0.05) in the plasma peak of the non-metabolizable glucose analogue 3-O-methylglucose and conversion of the expected postprandial rise in serum triglycerides (with saline 1.02 ± 0.20 to 1.51 ± 0.28 mmol/l, P < 0.05) to a decrease below basal values (with SMS 201–995 0.97 ±0.80 to 0.79 ± 0.11 mmol/l, P < 0.05).

4. After SMS 201–995, an enhancement of the increase in blood glucose (8.2 ±0.7 vs 4.7 ±0.2 mmol/l, P < 0.01) and inhibition and postponement of the postprandial rise in insulin (27.6 ±6.7 vs 9.9 ±2.1 m-units/l, P < 0.05) occurred. Furthermore, a rise in non-esterified fatty acids, glycerol and 3-hydroxybutyrate, compared with the decline in concentrations of these metabolites after saline, was observed.

5. We conclude that SMS 201–995 has actions to increase mouth-to-caecum transit time, to diminish the rate of active monosaccharide absorption and to lower basal and postprandial triglyceride levels. These effects probably relate to inhibition of exo- and endo-crine gastrointestinal secretion.
Mechanism of the postural vasoconstrictor response in the human foot
Authors: Hassan Ahmad A. K. , Tooke J. E.
Published: August 2015

1. The mechanism of postural vasoconstriction in the skin of the foot was examined in 102 healthy subjects by using laser Doppler flowmetry.

2. In 45 subjects, when one foot was lowered 50 cm below heart level and the other foot kept horizontal, blood flow was progressively reduced in the dependent foot (by 79%) with a concomitant, but less pronounced, reduction in flow in the horizontal foot (by 18%), indicating that a central mechanism is involved. After lumbar sympathetic blockade (in 10 patients with epidural anaesthesia), the flow in the horizontal foot remained virtually constant, indicating that the central component is mainly mediated via efferent sympathetic nerves, whereas the postural fall in flow in the dependent foot, though partially attenuated, was preserved, indicating that a local mechanism is mainly involved.

3. On lowering one foot below heart level in 12 subjects, there was a small but significant reduction in systolic and mean arterial pressures during the first minute of dependency. During the fourth minute, systolic pressure decreased, diastolic pressure and heart rate increased, but the mean arterial pressure was maintained.

4. In 19 subjects postural vasoconstriction was nearly abolished during local nervous blockade (lignocaine 3.7 × 10−4–7.4 × 10−2 mol/l), indicating that the local mechanism mediating the vasoconstriction is mainly neurogenic in nature. However, there was still a small fall (19%) in flow in the dependent foot during blockade, probably indicating a minor contribution of a local myogenic mechanism.

5. In three subjects, application of venous occlusion of 40 mmHg with the foot at heart level reduced the flow by 63% at rest, and by only 12% during local nervous blockade, indicating that the increased venous pressure on dependency provides the main stimulus for postural vasoconstriction. However, a greater reduction in flow was observed in 13 subjects when the foot was lowered 50 cm below the heart (75%) than during venous occlusion of 40 mmHg (52%) with foot at heart level, indicating that not only the increase in venous pressure but also the increase in arterial transmural pressure is implicated in the postural increase in precapillary resistance.

6. It is concluded that postural vasoconstriction in the human foot is mainly produced by a local neurogenic mechanism with a small contribution from a local myogenic response, in addition to a centrally elicited sympathetic component.
Hyponatraemia in quadriplegic patients
Authors: Leehey David J. , Picache Alicia A. , Robertson Gary L.
Published: August 2015

1. Studies were performed in five hyponatraemic (plasma sodium 129 ±1.6 mmol/l; plasma osmolality 268 ±3.0 mosmol/kg) quadriplegic patients in order to elucidate its aetiology. Five age- and sex-matched healthy subjects served as controls.

2. Daily urine volumes were high (4454 ± 624 ml) in the quadriplegic patients secondary to habitually increased fluid intake.

3. All quadriplegic patients had suppressed plasma arginine vasopressin levels (< 0.8 pmol/l) and were able to form dilute urine after a water load (20 ml/kg). However, free water clearance and the ability to excrete the water load were frequently impaired, and these defects were associated with reductions in both osmolar clearance and delivery of filtrate to the distal diluting sites of the nephron.

4. During hypertonic saline (5%, w/v, NaCl) infusion, plasma arginine vasopressin rose progressively before plasma osmolality reached the normal range, consistent with a resetting of the osmostat.

5. We conclude that hyponatraemia in quadriplegic patients is related to an intrarenal defect in water excretion and resetting of the osmostat coupled with increased fluid intake.
Changes in glomerular filtration rate, lithium clearance and plasma protein clearances in the early phase after unilateral nephrectomy in living healthy renal transplant donors
Authors: Strandgaard S. , Kamper A. , Skaarup P. , Holstein-Rathlou N. H. , Leyssac P. P. , Munck O.
Published: August 2015

1. Glomerular and tubular function was studied before and 2 months after unilateral nephrectomy in 14 healthy kidney donors by measurement of the clearances of 51Cr-labelled ethylenediaminetetra-acetate, lithium, β2-microglobulin, albumin and immunoglobulin G.

2. The glomerular filtration rate (GFR) of the kidney that remained in the donor rose from 45 ± 10 (mean ± sd) to 59 ± 10 ml/min (P < 0.01) 5 days after contralateral nephrectomy and remained at this level through the observation period.

3. The lithium clearance (CLi) of the remaining kidney rose from 11.6 ± 3.7 to 20.5 ± 8.2 ml/min (P < 0.01) and remained significantly elevated throughout the observation period.

4. Absolute proximal fluid reabsorption rate (APR), which was estimated as GFR minus CLi, was unchanged 5 days after contralateral nephrectomy, but then rose gradually to reach significantly elevated levels after 4 weeks.

5. Fractional proximal reabsorption (FPR; APR/GFR) fell from 0.75 ± 0.06 to 0.66 ± 0.11 (P < 0.01) but subsequently rose to levels not significantly decreased from normal.

6. Twenty-four hour fractional clearances of β2-microglobulin, albumin and immunoglobulin G rose markedly on the day of nephrectomy, peaked at 2–3 days and subsequently fell to moderately elevated levels.

7. Both the CLj and the plasma protein clearance studies demonstrate that the early response of the remaining kidney to contralateral nephrectomy in man is an increase in GFR, an unchanged APR and a fall in FPR. The proximal tubules thus initially handle the increased filtrate load by passing it on to more distal nephron segments. Within 2–4 weeks, an adaptive increase is seen in proximal reabsorption of both protein and fluid, resulting in an almost complete normalization of glomerulotubular balance.
Effects of frusemide and captopril on the relationship between biologically and immunologically active renin in human plasma
Authors: Higaki Jitsuo , Ogihara Toshio , Kumahara Yuichi
Published: August 2015

1. The plasma renin concentration (PRC) and active renin concentration determined by radioimmunometric assay (ARC) were measured before and after administration of frusemide or captopril to normal volunteers.

2. Injection of 40 mg of frusemide followed by 1 h in the upright position significantly increased both PRC (P < 0.001) and ARC (P < 0.001). Oral administration of 50 mg of captopril also increased PRC (P < 0.05) and ARC (P < 0.05).

3. ARC and PRC were linearly correlated in the basal supine position [y = 0.635 x − 0.048 (y = PRC, x = ARC), r = 0.958, P < 0.001], after frusemide injection and standing (y = 0.800x + 0.359, r = 0.793,P < 0.02) and after captopril administration in the supine position (y = 0.938x − 0.555, r = 0.998,P < 0.001).

4. A cross-calibration study in which pure human renin was added to pooled plasma and PRC and ARC were measured showed linearity between the values obtained by the two methods.

5. The regression line for values of PRC and ARC in the supine position after captopril administration had a significantly greater slope (P < 0.001) and that for values after frusemide injection and standing was significantly elevated (P < 0.001) compared with the regression line for basal values in the supine position.

6. These results show that the biological activity of renin may be increased by various acute stimulations of renin to inappropriately high levels compared with the immunological activity. This implies that the mode of processing of human plasma renin may be altered by acute stimulation of renin. Furthermore, current methods for assay of plasma active renin may give erroneous values in various pathophysiological conditions.
Urinary albumin excretion and blood pressure in the general population
Authors: Gosling Peter , Beevers D. G.
Published: August 2015

1. Twenty-four hour urinary albumin excretion rate was measured by a sensitive radioimmunoassay in 99 male and 100 female randomly selected factory workers, aged between 20 and 60 years.

2 The median (range) albumin excretion rates for men and women of 4.67 (1.0–25.8) and 5.25 (0.2–33.0) mg/24 h, respectively, were not significantly different.

3. No correlation was established between diastolic, systolic or mean arterial blood pressure and albumin excretion rate for the whole group.

4. Twenty-eight subjects with systolic and/or diastolic blood pressures ≥ 140/90 mmHg (18.7/12.0 kPa) showed a positive correlation between mean arterial blood pressure and albumin excretion rate (r = 0.412,P < 0.01).

5. There was no significant relationship between number of cigarettes smoked, age or alcohol intake and albumin excretion rate.

6. The data suggest that in the general population albumin excretion rate is variable and not dependent on blood pressure, but at blood pressures > 140/90 mmHg (18.7/12.0 kPa) albumin excretion rate may become pressure dependent, although high albumin excretion rates were sometimes found in subjects with blood pressures < 140/90 mmHg (18.7/12.0 kPa).
Plasma levels of the lyso-derivative of platelet-activating factor are related to age
Authors: Taylor Roger R. , Sturm Marian , Kendrew Philip J. , Vandongen Robert , Beilin Lawrence J.
Published: August 2015

1. The effect of age on the plasma level of the lyso-derivative of platelet-activating factor (lyso-PAF) was studied in 72 normal subjects, (32 females, 40 males) aged 12–64 years. Lyso-PAF was acetylated in vitro to PAF which was measured by bioassay using 5-[14C]hydroxytryptamine-labelled rabbit platelets.

2. Under 40 years there were similar direct relations between plasma lyso-PAF and age in both sexes (linear regression; males, P < 0.001; females, P < 0.002), the level approximately doubling from the adolescent level around 100 ng/ml. However, in the later years the levels fell, the fall seeming to commence earlier in females, so that between 40 and 65 years the level was greater in males [169 ± 47(sd) vs 120 ± 30 ng/ml; P < 0.01].

3. The increase in plasma lyso-PAF up to middle-age may be related to the reported increase in prostanoid production with age, since these platelet and vasoactive compounds can have a common origin in membrane phospholipid. This would be consistent with increasing phospholipase A2 activity and decreasing stability of cell membranes with age, but the later fall in lyso-PAF is then unexplained; the lesser values in females than males in the more advanced years could be related to females' generally lesser vascular disease. However, knowledge of the biological roles and metabolism of PAF is still very limited and the real significance of the findings remains to be determined.
Anaemia and reduced exercise capacity in patients on chronic haemodialysis
Authors: Mayer G. , Thum J. , Graf H.
Published: August 2015

1. In order to evaluate the influence of varying degrees of anaemia on exercise capacity and haemodynamic parameters, 13 patients on chronic intermittent haemodialysis with haemoglobin levels between 5.1 and 12.2 g/100 ml were subjected to an exhaustive exercise test. Measurements during bicycle ergometry consisted of O2 uptake at the anaerobic threshold and of maximum O2 uptake. Resting haemodynamic parameters such as cardiac index, heart rate, stroke volume index and blood pressure were assessed non-invasively in the 13 patients undergoing exercise and in an additional three patients.

2. O2 uptake at the anaerobic threshold as well as maximum peripheral O2 uptake were severely impaired and were positively correlated with haemoglobin concentration. The strongest correlation was found between the impairment of O2 uptake at maximum workload, as assessed by maximum O2 uptake/predicted maximum O2 uptake, and haemoglobin concentration. Haemodynamic alterations in the resting state consisted of a cardiac index in the upper normal range and did not correlate with the haemoglobin concentration.

3. We conclude from our study that exercise capacity in patients on chronic intermittent haemodialysis is severely impaired and that the impairment of aerobic and anaerobic capacity is significantly correlated with the severity of renal anaemia.
Metabolic characteristics of human adipose tissue in vivo
Authors: Frayn K. N. , Coppack S. W. , Humphreys S. M. , Whyte P. L.
Published: August 2015

1. A method was developed for sampling the venous drainage from the subcutaneous adipose tissue of the anterior abdominal wall. This is a large depot in many subjects, and seems well suited to such studies as it is completely separated from the venous drainage of the underlying muscle by the aponeurosis of the external oblique muscle.

2. Eight normal subjects were studied after an overnight fast, and for 120 min after ingestion of 75 g of glucose. Concentrations of substrates in the abdominal wall drainage were compared with those in arterialized blood and in forearm muscle drainage.

3. Non-esterified fatty acid and glycerol concentrations in the abdominal wall drainage were high (three to four times the arterial level) after overnight fast. After glucose ingestion, arterial and abdominal venous levels fell and the arteriovenous differences narrowed. The forearm showed uptake of non-esterified fatty acids when fasting but not after glucose ingestion, with no significant arteriovenous difference for glycerol at any time.

4. The abdominal wall tissues showed a small arteriovenous difference for glucose uptake during fasting, which increased after glucose ingestion. Although lactate was produced throughout, its molar ratio to glucose uptake was less than that reported for other superficial sites, suggesting only a minor contribution of skin metabolism. Forearm muscle showed a larger and more prolonged increase in arteriovenous difference for glucose uptake after the glucose load, but no consistent release or uptake of lactate.

5. We conclude that the tissue studied by this technique is predominantly adipose. This technique may have wide application in studies of the metabolic basis for body weight regulation in man.
Platelet efflux of noradrenaline in patients with type 1 diabetes mellitus
Authors: Smith C. C. T. , Wilson A. P. , Prichard B. N. C. , Betteridge D. J.
Published: August 2015

1. Endogenous noradrenaline release from washed platelets incubated under resting conditions and in the presence of thrombin was examined in 14 normal subjects and 10 subjects with type 1 (insulin-dependent) diabetes.

2. Irreversible aggregation of platelets from both normal and diabetic subjects was induced by thrombin (0.3 unit/ml). Platelets from diabetic subjects were more sensitive than platelets from normal subjects, extents of aggregation being 89% and 76%, respectively (P < 0.002).

3. Stimulation with thrombin (0.3 unit/ml) elicited marked platelet release of noradrenaline to the incubation medium in both normal and diabetic subjects. Supernatant noradrenaline concentrations obtained under thrombin-stimulated conditions did not significantly differ between normal and diabetic subjects. However, under resting conditions noradrenaline levels were significantly greater (+ 93%, P < 0.02) for diabetic than normal subjects.

4. Measurement of platelet noradrenaline contents after thrombin stimulation revealed no difference between normal and diabetic subjects. Under resting conditions, however, platelet noradrenaline levels were significantly lower (−46%, P < 0.02) for diabetic than normal subjects. Thus, in the diabetic subjects increased resting platelet efflux of noradrenaline is mirrored by a decreased platelet noradrenaline content.

5. A consequence of increases in resting catecholamine efflux may be enhanced platelet activity resulting in increased platelet aggregation.
Differential effect of high-dose naloxone on the plasma adrenaline response to the cold-pressor test
Authors: Bouloux P. M. G. , Newbould E. , Causon R. , Perry L. , Rees L. H. , Besser G. M. , Grossman A.
Published: August 2015

1. Although the opiate antagonist naloxone has been shown to affect sympathoadrenomedullary function in some studies, this has not been a uniform finding in all investigations, using different doses of naloxone. We have therefore investigated the actions of saline placebo and increasing bolus doses of intravenous naloxone (25, 100 and 250 μg/kg) on the plasma noradrenaline, adrenaline, adrenocorticotrophin (ACTH) and cortisol responses to a cold-pressor test in six males and two females in a double-blind randomized study.

2. Basal levels of adrenaline did not differ on any of the study occasions: the cold-pressor stimulus produced a significant rise in mean plasma adrenaline to a peak of 0.16 nmol/l, with a peak incremental rise of 0.08 nmol/l. In the presence of the two higher doses of naloxone, the incremental rise in the mean adrenaline level was significantly enhanced, reaching 0.30 nmol/l at 100 μg of naloxone/kg and 0.29 nmol/l at 250 μg of naloxone/kg, with no significant enhancement observed at the lowest dose of naloxone. The rise in plasma noradrenaline, systolic and diastolic blood pressure and pulse rate during the cold-pressor test was not consistently altered by any dose of naloxone, but there was a significant trend for the degree of discomfort to increase with the dose of naloxone.

3. Neither plasma ACTH nor serum cortisol rose in response to the cold-pressor stimulus. Analysis of variance demonstrated a significant naloxone-treatment effect for both ACTH and cortisol, with the 100 μg/kg and 250 μg/kg doses of naloxone leading to a significant rise in mean plasma ACTH not seen at the lowest dose of 25 μg/kg.

4. In a separate study of the effect of naloxone on the clearance of plasma adrenaline, adrenaline was infused on two occasions into eight normal male subjects to a maximum dose of 5 μg/min for 15 min, and blood was sampled at regular intervals during and after termination of the infusion, preceded by 8 mg of naloxone or placebo. After termination of the adrenaline infusion, there was a rapid fall in plasma adrenaline (Λ = −1.9 ± 0.3 min), which was not altered by naloxone (Λ = −1.8 ± 0.3 min).

5. We conclude that the potentiation of the adrenaline response to a cold-pressor test by naloxone is mediated by increased secretion of adrenaline and not by a reduction in its clearance rate, and that this response is of low naloxone sensitivity.
Haemodynamic responses to vasopressin in anaesthetized young and adult Brattleboro rats
Authors: Obika L. F. O. , Laycock J. F.
Published: August 2015

1. The cardiovascular effects of pressor doses of arginine vasopressin were examined in anaesthetized Brattleboro rats with hereditary diabetes insipidus (BDI) and normal rats of the parent Long Evans (LE) strain, either 37 or 85 days old.

2. Control mean arterial blood pressure and total peripheral resistance were similar in adult animals of the two strains but were significantly lower in the young BDI rats compared with the young LE rats.

3. The three doses of vasopressin produced greater pressor responses in the young, immature LE rats compared with the young BDI rats, whereas in the adult animals vasopressin had the greater pressor effect in the BDI rats compared with the LE rats of comparable age.

4. There was little effect of vasopressin on cardiac output after the initial decrease, particularly in the BDI rats whether immature or adult, despite more prolonged decreases in heart rate.

5. These studies indicate important age-related differences in the pressor response to vasopressin in anaesthetized rats, in addition to the clear differences in response between the animals with (LE) or without (BDI) the circulating endogenous peptide.
Coumarin and 7-Hydroxycoumarin Treatment of Canine Obstructive Lymphoedema
Authors: Knight Kenneth R. , Khazanchi Rakesh K. , Pederson W. Christopher , McCann John J. , Coe Serena A. , O'Brien Bernard McC.
Published: August 2015

1. Canine obstructive lymphoedema was created in one hind leg of 30 dogs by irradiation of the groin and surgical removal of surviving lymph glands and lymphatics. The opposite leg served as a control. Once the oedema had stabilized, groups of 10 dogs were treated orally with 12.5 mg day−1 kg−1 for 8 months with either one of the benzopyrones coumarin (2H-1-benzopyran-2-one) and 7-hydroxycoumarin (7-hydroxy-2H-1-benzopyran-2-one), or placebo.

2. The two benzopyrones significantly (P < 0.01) but gradually reduced the oedema by 20–30% over 8 months, as judged by circumferential measurements of the oedematous and control limbs. There was no change with the placebo.

3. In the oedematous fluids (lymph and interstitial fluid), benzopyrone treatment reduced the protein content and increased acid and neutral proteinase activity compared with the control limbs, while the levels of the proteinase inhibitor α2-macroglobulin remained unchanged. Furthermore, these active drugs reduced the excess water content, thickness and hydroxyproline content of skin biopsies from oedematous limbs compared with those from control limbs. No changes were observed for the placebo group.

4. These biochemical changes suggest that benzopyrones can reduce the excess proteinaceous fluid in lymphoedema by increasing the levels of proteinase activity relative to the number of proteinase inhibitors. As a secondary event the amount of fibrosis in the skin is also reduced, presumably by an increase in collagenase activity from the mononuclear phagocytes.

5. These results support the hypothesis that benzopyrones activate the production of proteinases by mononuclear phagocytes. The resultant small peptides can drain locally into the bloodstream, thus bypassing the blocked lymphatics and reducing the protein concentration and its associated oedema fluid.
The 57 mm Thermal Clearance Probe: A Non-Invasive Tool for Measuring Subcutaneous Blood Flow
Authors: Greenhalgh P. M. , Jones J. R. , Yudkin J. S.
Published: August 2015

1. The segmented thermal clearance probe is a noninvasive instrument which measures heat thermal clearance, a variable directly proportional to superficial blood flow, with a depth sensitivity theoretically proportional to the sensor diameter. We compared an 18 mm sensor and a recently developed 57 mm sensor with the reference technique of xenon washout.

2. The theoretical depth sensitivity of the sensors was assessed using Perspex spacers. Ninety-five per cent of sensitivity had been lost at the respective depths of 3.5 mm and 7.1 mm for the 18 mm and 57 mm sensors.

3. A comparison was made between heat thermal clearance reading and 133Xe decay curves using the two probes for 15 min after injection of 133Xe at 2 mm and 6 mm depths in the anterior thigh in 41 subjects. The 57 mm sensor showed similar correlation with xenon washout at 2 mm injection depth (r = 0.89) and 6 mm injection depth (r = 0.86), whereas the 18 mm sensor showed greater correlation at 2 mm (r = 0.92) than at 6 mm (r = 0.62).

4. The 57 mm sensor was compared with xenon washout at 6 mm in eight insulin-treated diabetic subjects. The relationship was similar to that in non-diabetic subjects (r = 0.79), with no significant difference in slope or intercept.

5. It is concluded that the 57 mm thermal clearance probe may be used to study blood flow at the depth of insulin injection (6 mm) in diabetic and non-diabetic subjects.
Effect of Catecholamines and Insulin on Plasma Volume and Intravascular Mass of Albumin in Man
Authors: Hilsted J. , Christensen N. J. , Larsen S.
Published: August 2015

1. The effect of intravenous catecholamine infusions and of intravenous insulin on plasma volume and intravascular mass of albumin was investigated in healthy males.

2. Physiological doses of adrenaline (0.5 μg/min and 3 μg/min) increased peripheral venous packed cell volume significantly; intravenous noradrenaline at 0.5 μg/min had no effect on packed cell volume, whereas packed cell volume increased significantly at 3 μg of noradrenaline/min. No significant change in packed cell volume was found during saline infusion.

3. During adrenaline infusion at 6 μg/min, packed cell volume increased, plasma volume decreased and intravascular mass of albumin decreased significantly. During noradrenaline infusion at 6 μg/min, packed cell volume increased and plasma volume decreased, but intravascular mass of albumin did not change.

4. Application of a hyperinsulinaemic, euglycaemic glucose clamp led to an increase in transcapillary escape rate of albumin and a decrease in intravascular mass of albumin. Packed cell volume remained constant, while plasma volume, measured by radiolabeled albumin, decreased.

5. We conclude that the previously reported changes in packed cell volume, plasma volume, intravascular mass of albumin and transcapillary escape rate of albumin during hypoglycaemia may be explained by the combined actions of adrenaline and insulin.
Problems in Measuring Human Leucocyte Cation Content: Effects of Cell Preparation and Handling
Authors: Main J. , Thomas T. H. , Wilkinson R.
Published: August 2015

1. Previous published measurements of leucocyte cation content are inconsistent, with sodium concentrations having particularly high coefficients of variation. We have measured the effects of recovery time after isolation, different types of handling, and centrifugation on leucocyte sodium and potassium content.

2. Sodium content fell markedly during the first 30 min after isolation and was stable from 1 to 3 h of incubation. There was a small but significant rise in potassium content over the same time period.

3. During incubation, occasional gentle resuspension of the cells gave optimal sodium contents, whereas mixing by inversion caused large falls in sodium and potassium content.

4. Centrifugation of stable cells at 200 g for 6 min caused marked increases in sodium content.
Lipoxin A4 and Lipoxin B4 Inhibit Chemotactic Responses of Human Neutrophils Stimulated by Leukotriene B4 and N-Formyl-l-Methionyl-l-Leucyl-l-Phenylalanine
Authors: Lee Tak H. , Horton Claire E. , Kyan-Aung U. , Haskard Dorian , Crea Atttlio E. G. , Spur Bernd W.
Published: August 2015

1. Lipoxin A4 (LXA4) and lipoxin B4 (LXB4) have been evaluated for their capacities to modulate neutrophil (PMN) migration and endothelial cell adherence using compounds prepared by total chemical synthesis.

2. Increased PMN migration was seen with concentrations of LXA4 from 10−9 mol/l to 10−7 mol/l. LXA4 was 100-fold less potent than leukotriene B4 (LTB4) and it elicited only one-half of the maximal response of LTB4.

3. The (5S,6S,15S)-isomer of LXA4 induced only a weak migratory response and LXB4 was inactive, suggesting that the activity of LXA4 was stereospecific.

4. Modified chequerboard analysis indicated that LXA4 was a chemokinetic agent.

5. Preincubation of PMN with increasing concentrations of LXA4 induced a very similar dose- and time-dependent inhibition of the subsequent response to 10−7 mol/l LTB4 or 10−7 mol/l N-formyl-l-methionyl-l-leucyl-l-phenylalanine (FMLP). The inhibition was observed at 10−10 mol/l LXA4; the concentration which produced 50% inhibition was 10−8 mol/l and 100% inhibition of PMN locomotion occurred at 10−6 mol/l LXA4.

6. The (5S,6S,15S)-isomers of LXA4 and LXB4 were 5- and 100-fold less potent than LXA4, respectively, in suppressing LTB4- or FMLP-induced PMN migration.

7. Preincubation of PMN with LXA4 led to a suppression of calcium mobilization, as assessed by Quin2-AM fluorescence, when the cells were subsequently stimulated under optimal conditions by LTB4 or FMLP.

8. These results suggest that the inhibitory activity of lipoxins may be related to the capacity of these molecules to regulate calcium ion mobilization.

9. LXA4 and LXB4 did not promote PMN adherence to human endothelial cell monolayers and they did not modulate FMLP-stimulated PMN-endothelial cell adhesion.
Effects of Underfeeding and of Starvation on Thermoregulatory Responses to Cooling in Women
Authors: Mansell P. I. , Macdonald I. A.
Published: August 2015

1. The effects of acute alterations in energy intake on the thermoregulatory responses to a cooling stimulus were studied in healthy, normal weight, young female subjects. On separate occasions, seven subjects were underfed for 7 days at 60 kJ day−1 kg−1 ideal body weight and six subjects were starved for 48 h. The cooling stimulus was provided by a coverall perfused with water at 16°C.

2. After the application of the cooling stimulus, central body (auditory canal) temperature rose initially in both studies. After underfeeding, the magnitude of this rise in temperature was not significantly different from that seen in the normally fed state. After 48 h starvation, the rise in temperature on cooling was reduced from 0.30 (sem 0.03) to 0.10 (0.04)°C (P < 0.01). In two subjects in whom central body temperature had been maintained in the normally fed state, a fall occurred after starvation.

3. Underfeeding for 7 days did not affect thermogenesis or the degree of vasoconstriction in the forearm or hand in response to cooling.

4. After 48 h starvation, the thermogenic response to cooling was abolished and blood flow in the forearm remained higher than in the normally fed state.

5. In normal weight young females, thermoregulatory responses to a cooling stimulus were therefore substantially affected by 48 h starvation but not by 7 days underfeeding.
Hepatic and Peripheral Insulin Action in Chronic Renal Failure before and during Continuous Ambulatory Peritoneal Dialysis
Authors: Heaton A. , Taylor R. , Johnston D. G. , Ward M. K. , Wilkinson R. , Alberti K. G. M. M.
Published: August 2015

1. A three-step hyperinsulinaemic euglycaemic clamp was performed in six uraemic patients before dialysis and after 3 months of treatment with continuous ambulatory peritoneal dialysis, and in seven matched normal control subjects. Glucose turnover was assessed basally and during the clamp using [3-3H]glucose as a tracer.

2. The glucose infusion rate required to maintain euglycaemia was insignificantly higher in normal subjects compared with undialysed uraemic subjects at each insulin infusion rate.

3. The isotopically assessed total glucose turnover was also similar in normal and uraemic subjects. Basal hepatic glucose output was again similar in uraemic and control subjects and output was suppressed to a similar degree at each insulin infusion rate.

4. After treatment with continuous ambulatory peritoneal dialysis, the glucose infusion rate and the total glucose turnover during the clamp rose significantly at all three insulin concentrations (P < 0.05), but remained insignificantly different from normal control values. Hepatic glucose output was unchanged.

5. Peripheral insulin action was improved during continuous ambulatory peritoneal dialysis, but hepatic insulin action was unchanged.
Atrial Natriuretic Factor Content of Brain Nuclei in Deoxycorticosterone Acetate-Salt Hypertension in the Rat
Authors: Geiger Helmut , Bahner Udo , Palkovits Miklos , Hupe Jürgen , Heidland August
Published: August 2015

1. The influence of deoxycorticosterone acetate (DOCA)–salt hypertension on brain atrial natriuretic factor (ANF) in rats was investigated to elucidate the role of central ANF in a renin-independent model of experimental hypertension.

2. Sprague-Dawley rats were subjected to uninephrectomy and given either tap water or saline [1% (w/v) NaCl] to drink plus weekly injections of either saline or DOCA (25 mg/kg, subcutaneously). After 32 days, the rats were decapitated and 18 different brain nuclei were removed by a micropunch technique.

3. The systolic blood pressure of the DOCA-salt rats was significantly higher than that of control rats [154 ± 3 mmHg vs 104 ± 2 mmHg (20.53 ± 0.40 kPa vs 13.86 ± 0.27 kPa), P < 0.001].

4. Plasma ANF levels were significantly (P < 0.01) higher in DOCA-salt hypertensive rats compared with control rats.

5. In DOCA-salt hypertensive rats, the ANF content was increased in the organum vasculosum of the lamina terminalis (31.4 ± 2.1 vs 22.1 ± 2.5 pg/mg of protein, P < 0.05), the subfornical organ (32.5 ± 5.0 vs 24.2 ± 2.4 pg/mg of protein, P < 0.05), the medial amygdaloid nucleus (49.0 ± 6.4 vs 34.0 ± 2.0 pg/mg of protein, P < 0.05) and the locus coeruleus (86.9 ± 4.1 vs 64.4 ± 4.2 pg/mg of protein, P < 0.01) compared with control rats. The ANF content of 14 other brain areas investigated did not alter after treatment.

6. Our data demonstrate that the development of DOCA-salt hypertension in rats is associated with changes in the ANF content of specific brain areas, especially the locus coeruleus, and is consistent with an important pathophysiological role of this pontine area in the development of DOCA-salt hypertension.