bluuebunny/crossref_metadata_2025 huggingface dataset:
Biochemical and Morphometric Properties of Mitochondrial Populations in Human Muscle Fibres
Authors: Elander Anna , Sjöström Michael , Lundgren Fredrik , Scherstén Tore , Bylund-Fellenius Ann-Christin
Published: August 2015

1. Two mitochondrial subpopulations were evaluated with biochemical and morphological techniques in human gastrocnemius muscle of 10 patients with peripheral arterial insufficiency and 12 control individuals.

2. The subsarcolemmal mitochondria were released by gentle homogenization, with a recovery of 32-37%, and the intermyofibrillar by enzymic digestion and further mechanical disintegration, recovery 18-21%. The subsarcolemmal mitochondria were morphologically defined as those located within 2 μm from the sarcolemma membrane and the intermyofibrillar mitochondria as those located in the rest of the fibre.

3. In the controls the intermyofibrillar mitochondria had a lower respiratory ratio than the subsarcolemmal, owing to a higher state II respiration. The subsarcolemmal space, which contained 25% of the mitochondria, had a mitochondrial volume density two- to three-fold that of the intermyofibrillar space in the controls.

4. The patients, who had a 48-64% higher oxidative enzyme capacity in their muscle tissue, had higher respiratory rate and respiratory control index with similar ADP/O ratio in the subsarcolemmal fraction in comparison with the controls. The citrate synthase activity was higher in both mitochondrial fractions of the patients. The volume densities of mitochondria, total as well as for both subpopulations, were also higher in the patients, which was further reflected in higher yields of mitochondrial protein.

5. The results demonstrate that both sub-populations of muscle mitochondria are able to adapt quantitatively and/or qualitatively. Furthermore, they show that the increased oxidative enzyme capacity of the patients is associated with an increased quantity of both mitochondrial populations and a qualitative improvement of the respiratory activity of the subsarcolemmal mitochondria.
Maximal short term Exercise Capacity in Healthy Subjects Aged 15-70 Years
Authors: Makrides Lydia , Heigenhauser George J. F. , Mccartney Neil , Jones Norman L.
Published: August 2015

1. Fifty males and 50 females, 15-71 years of age, exercised maximally for 30 s on an isokinetic ergometer at a pedalling frequency of 60 rev./min. Results were compared with maximal oxygen uptake (VO2 max.) obtained in a progressive incremental exercise test.

2. Total work in 30 s was higher in males than females, declined linearly by about 6% per decade of age (r = −0.65), and was related closely to height (r = 0.75) and to lean thigh volume estimated anthropometrically (r = 0.84). A close association with vital capacity (r = 0.86) was also found that accounted statistically for the combined effects of age and height.

3. The percentage decline in power during 30 s (fatigue index) was lower in subjects reporting greater leisure activity.

4. A close relationship was found between total work in 30 s and Vo2 max. (r = 0.86), with vital capacity and leisure activity exerting additional influences on Vo2 max. (P < 0.001; multiple r = 0.93).

5. The well-established reduction with age in Vo2 max. is associated with an apparent parallel reduction in the power output capacity of large muscle groups recruited in heavy dynamic leg exercise.
Effects of Synthetic Atrial Natriuretic Peptides on Sodium-Potassium Transport in Human Erythrocytes
Authors: Sagnella G. A. , Nolan D. A. , Shore A. C. , MacGregor G. A.
Published: August 2015

1. The effects of synthetic human and rat atrial peptides on sodium and potassium ion transport has been investigated in intact human erythrocytes.

2. The effects of these peptides have been tested on the active, sodium pump-dependent (ouabain-sensitive) and on the sodium-potassium cotransport system (bumetanide-sensitive) with 86Rb used as a tracer.

3. Human (α-ANP, 28 amino acids) or rat (atriopeptin III) atrial peptides, over a wide range of concentrations, did not influence the uptake of 86Rb in either the ouabain-sensitive or the bumetanide-sensitive transport system.

4. These results suggest that the natriuretic effect of the atrial peptides is not mediated through inhibition of the sodium pump or the loop-diuretic-sensitive Na-K cotransport.
α-Adrenoceptor Changes after Oestrogen Treatment in Platelets and other Tissues in Female Rabbits
Authors: Mishra N. , Hamilton C. A. , Jones C. R. , Leslie C. , Reid J. L.
Published: August 2015

1. α2-Adrenoceptors on blood platelets have been widely used as a model for α-adrenoceptors in less accessible tissues.

2. The effect of oestrogen (200 μg/day intramuscularly) on α2-adrenoceptor number and function was studied in immature female rabbits. α2-Adrenoceptor number was measured in whole platelets, and membrane preparations of forebrain, hindbrain, spleen and kidney by radioligand binding. α2-Adrenoceptor function was examined by measuring platelet aggregation in vitro and circulatory responses to selective α2-adrenoceptor agonists in vivo.

3. Oestrogen treatment resulted in a significant decrease in platelet α2-adrenoceptor number and function. However, no changes were observed either in receptor number in other tissues or in responses to α2-agonists in vivo.

4. The results suggest that oestrogen modulation of rabbit platelet α2-adrenoreceptor number and function may be different from that of brain, kidney and spleen. Caution should be exercised in extrapolating results from platelets to α-adrenoceptors at other sites.
Increased albumin and normal dextran clearances in protein-overload proteinuria in the rat
Authors: Bliss David J. , Brewer Douglas B.
Published: August 2015

1. Female Wistar rats were made heavily proteinuric by daily intraperitoneal injections of bovine serum albumin over 5 days.

2. The size and charge permeability characteristics of the glomerular filter in this condition were determined by studying the renal handling of poly-dispersed uncharged dextran over the range of molecular radii 2–6 nm (albumin 3.6 nm), and of endogenous rat serum albumin over the same clearance period.

3. In proteinuric rats the clearance of rat serum albumin was significantly increased with a resultant reduction in the circulating levels of rat serum albumin. The clearance of uncharged dextran was not significantly different in proteinuric rats compared with control animals.

4. There does not appear to be any size selective defect of the glomerular filtration barrier in this condition. This suggests that the observed increase in the clearance of the negatively charged endogenous albumin may be due to a reduction in the glomerular charge barrier.
Ventilatory saving by external chest wall compression or oral high-frequency oscillation in normal subjects and those with chronic airflow obstruction
Authors: George R. J. D. , Winter R. J. D. , Flockton S. J. , Geddes D. M.
Published: August 2015

1. Oscillation of the air within the lungs at high frequency is associated with an increased clearance of CO2. Because of the high frequency and low volume of these oscillations, spontaneous breathing is unhindered and the technique has potential value as a supplement to ventilation.

2. High-frequency oscillations were superimposed upon tidal breathing by using a loudspeaker attached to a mouthpiece (oral high-frequency oscillation, OHFO) or by external chest wall compression (ECWC). We set out (a) to compare the changes in ventilation and breathlessness by using OHFO and ECWC in normal subjects with those in patients with chronic airflow obstruction (CAO), and (b) to relate the pattern of saving to the resonant frequencies of the respiratory system as a whole (fOT, 5–10 Hz in normal subjects, 16–26 Hz in CAO) and those of the ribcage(foc,70 Hz).

3. OHFO reduced minute ventilation (VE) by up to 46% in normal subjects (P < 0.01) and 29% in CAO (P < 0.01) without any rise in CO2. ECWC reduced VE by 27% in normal subjects (P < 0.01) and 16% in CAO (P < 0.01) without a rise in CO2.

4. High-frequency oscillation by either method relieved breathlessness in those with CAO and was comfortable and well tolerated.

5. In normal subjects for was discrete and varied little with respiration. Maximum savings occurred around for (5–10 Hz).

6. In CAO, there was no obvious single resonant frequency and flow and pressure signals were intermittently in phase over a band of about 10 Hz. Thus the reductions in minute ventilation were only loosely related to for (13–26 Hz). Neither group reduced VE at foc (65–75 Hz).

7. OHFO has considerable potential in the management of patients with CAO, where it may be of value as an assistance to breathing and in the relief of breathlessness. ECWC, although effective in principle, is impractical by our methods and awaits the development of an acceptable delivery system.
Changes in plasma free 3,4-dihydroxyphenylethylene glycol and noradrenaline levels after acute alcohol administration
Authors: Howes L. G. , Reid J. L.
Published: August 2015

1. The effects of alcohol (0.9 g/kg) compared with placebo (400 ml of orange juice) on plasma noradrenaline and 3,4-dihydroxyphenylethylene glycol levels, and on erect and supine blood pressures and heart rates, were studied in eight normal male volunteers.

2. Alcohol caused a rise in noradrenaline levels that commenced approximately 30 min after drinking and lasted about 4h. In contrast, 3,4-dihydroxyphenylethylene glycol levels fell immediately after alcohol administration and remained low for at least 6h. Acute alcohol administration alters noradrenaline catabolism, and may have a dual effect of increasing noradrenaline release and decreasing noradrenaline clearance.

3. Alcohol caused a transient rise in erect and supine blood pressures that preceded the rise in plasma noradrenaline. Thereafter erect blood pressures fell compared with control. This fall was associated with a progressive rise in both supine and erect rates, and reached a maximum several hours after the maximum levels of blood alcohol.

4. The major effect of acute alcohol administration is to lower blood pressure and induce a reflex tachycardia. Changes in noradrenaline and 3,4-dihydroxyphenylethylene glycol levels did not readily explain changes in blood pressure or heart rate, suggesting that alcohol induced changes in noradrenaline metabolism occur largely independent of changes in blood pressure and heart rate.
Twenty-four hour hormonal and metabolic profiles in uraemic patients before and during treatment with continuous ambulatory peritoneal dialysis
Authors: Heaton A. , Johnston D. G. , Haigh J. W. , Ward M. K. , Alberti K. G. M. M. , Kerr D. N. S.
Published: August 2015

1. Circulating intermediary metabolite and hormone concentrations were measured at intervals over 24 h in five uraemic patients before starting dialysis and after 3 months' treatment with continuous ambulatory peritoneal dialysis (CAPD) and in 13 non-uraemic normal controls.

2. Fasting and postprandial glucose concentrations were significantly raised in uraemic patients undialysed and on CAPD but 24 h mean (±sem) levels fell from 6.63 ± 0.40 to 6.00 ± 0.26 mmol/l (P < 0.02) after 3 months' dialysis despite peritoneal glucose absorption. Insulin levels were raised in uraemic patients but were unchanged by CAPD.

3. Uraemia was associated with raised levels of the gluconeogenic precursors lactate and alanine and a further rise in fasting and 24 h mean alanine concentrations occurred with CAPD. Fasting total ketone body concentrations were raised in undialysed uraemic patients but concentrations were suppressed throughout the 24 h in CAPD subjects.

4. Fasting triglyceride concentrations were increased in uraemic subjects and mean 24 h levels rose by 30% from 1.55 ± 0.42 mmol/l before dialysis to 2.02 ± 0.59 mmol/l during CAPD. Non-esterified fatty acid concentrations were low in uraemic patients and remained low during CAPD.

5. Undialysed and dialysed uraemic patients displayed raised plasma glucagon concentrations throughout the 24 h, suppression of the normal nocturnal secretion of growth hormone and raised mean cortisol levels, which were 23% (CAPD) to 57% (undialysed) higher than in normal controls.

6. The endocrine and metabolic abnormalities of uraemia are not fully corrected by CAPD. Many of the additional changes observed during CAPD reflect an adaptation to the constant absorption of peritoneal glucose.
Abnormal vascular function and morphology in preeclampsia: a study of isolated resistance vessels
Authors: Aalkjaer C. , Danielsen H. , Johannesen P. , Pedersen E. B. , Rasmussen A. , Mulvany M. J.
Published: August 2015

1. In order to obtain direct information about vascular changes associated with pre-eclampsia, the morphological and functional characteristics of isolated omental resistance vessels from 11 women with pre-eclampsia, 10 normotensive pregnant women and eight normotensive nonpregnant women were determined.

2. In vessels from the women with preeclampsia, the ratio of media thickness to lumen diameter was increased, compared with that in vessels from the other two groups.

3. The vessels from the women with preeclampsia had an increased responsiveness to angiotensin II and a decreased rate of relaxation, but only when compared with the vessels from the normotensive pregnant women. However, no difference in responsiveness to noradrenaline was found between any of the groups.

4. The angiotensin II responsiveness of the vessels from the women with pre-eclampsia and from the non-pregnant women were similar, suggesting that pre-eclampsia is associated with an absence of the change in vascular function which normally occurs during pregnancy.

5. The study provides direct evidence for an involvement of vascular abnormalities in the pathogenesis of pre-eclampsia.
Urinary prostaglandin E and antidiuretic hormone during water immersion in man
Authors: O'hare J. P. , Watson M. , Penney M. D. , Hampton D. , Roland J. M. , Corrall R. J. M.
Published: August 2015

1. In 10 normal subjects water immersion to the neck at 35°C produced a highly significant natriuresis and diuresis.

2. Urinary prostaglandin E levels did not change significantly throughout immersion.

3. During the diuresis of water immersion a suppression of urinary antidiuretic hormone occurred.
Effect of induced metabolic acidosis on intracellular pH, buffer capacity and contraction force of human skeletal muscle
Authors: Hultman E. , Del Canale S. , Sjöholm H.
Published: August 2015

1. Five volunteers were studied before and after oral administration of NH4Cl (0.3 g/kg body wt.) given in order to create a moderate acidosis.

2. The quadriceps femoris muscles were stimulated electrically for 75 s and muscle biopsies for determination of pH and metabolite content were taken before, at the end of contraction and after 10 min in the recovery period.

3. Muscle pH at rest (mean 7.04) was not significantly decreased after acidification despite an extracellular pH decrease of 0.15 unit.

4. After contraction muscle pH was significantly lower after NH4Cl. Mean values before and after acidification were 6.70 and 6.54 respectively.

5. The buffer capacity calculated as the total capacity of the muscle to buffer H+ produced during the isometric contraction before and after NH4Cl ingestion was reduced from 68.6 sl to 54.5 sl.

6. The force produced by contracting muscle was significantly lower at the end of the contraction period after NH4Cl ingestion, 44.6% of initial compared with 55.4% without NH4Cl.
Effects of acute and chronic treatment with glucocorticoids on the intestinal absorption of calcium and phosphate and on plasma 1,25-dihydroxyvitamin D levels in pigs
Authors: Fox John , Ross Richardus , Care Anthony D.
Published: August 2015

1. We have used young pigs, each prepared surgically with a Thiry-Vella loop of proximal small intestine, to study the time course of changes in the intestinal absorption of calcium, phosphate, sodium, glucose and water and on the plasma levels of 1,25-dihydroxyvitamin D after treatment of the animals with glucocorticoids.

2. Perfusion of the intestinal loop for 6 h with a solution containing hydrocortisone or betamethasone was without effect on the absorption of calcium or phosphate.

3. The oral administration of betamethasone stimulated the absorption of calcium and phosphate by 15–20% for 2–3 days before the trend was reversed and absorption was progressively reduced.

4. Chronic treatment with betamethasone inhibited only the active component of calcium and phosphate absorption.

5. Treatment with betamethasone was associated with a sustained 25–50% increase, to a maximum by 2 days, in the absorption of sodium, glucose and water.

6. Plasma levels of 1,25-dihydroxyvitamin D were reduced within 2 days of the start of treatment and reached a minimum (40–50% decrease) in 4–6 days.

7. We conclude that the initial stimulation of calcium and phosphate absorption is caused by the increased absorption of water. The long-term decrease in absorption may not be caused solely by the decreased circulating levels of 1,25-dihydroxyvitamin D since absorption continued to fall for several weeks after 1,25-dihydroxyvitamin D levels had reached a minimum.
Obstructive jaundice blunts myocardial contractile response to isoprenaline in the dog: a clue to the susceptibility of jaundiced patients to shock?
Authors: Binah O. , Bomzon A. , Blendis L. M. , Mordohovich D. , Better O. S.
Published: August 2015

1. Patients with obstructive jaundice are susceptible to postoperative shock. To clarify the mechanism of this phenomenon, we compared the contractile response to isoprenaline of isolated ventricular preparations from three groups of dogs: (a) dogs with chronic bile-duct ligation (CBDL), (b) dogs with choledochocaval anastomosis (CDCA) and (c) sham-operated dogs (SO).

2. Isolated ventricular muscles from CBDL and CDCA dogs showed a depressed contractile response to isoprenaline as compared with SO dogs. Mechanical performance was spared in the CBDL and CDCA dogs.

3. There were no differences in the contractile responses of SO and CBDL dogs, either to ouabain or to changes in the rates of stimulation (force-frequency relationships). These data demonstrate that, in the dog, obstructive jaundice and/or cholaemia are associated with blunted contractile response to β-adrenoreceptor stimulation in the face of intact basic mechanical performance.

4. Similar inotropic refractoriness to β-adrenoreceptor stimulation could contribute to the susceptibility to postoperative shock in patients with obstructive jaundice.
Validation of a method for measuring the short-term rate of urea synthesis after an amino acid load
Authors: Kay J. D. S. , Seakins J. W. T. , Geiseler D. , Hjelm M.
Published: August 2015

1. The response of the plasma concentration of urea to the oral and intravenous administration of alanine was studied in healthy adult humans.

2. The instantaneous rate of urea synthesis was calculated by using a model-dependent procedure. The errors in this procedure were calculated and it was shown that analytical precision and sampling frequency, and the estimates of the distribution volume and elimination fluxes, were adequate to determine the synthesis parameters.

3. A direct test of the compartmental model was made by the intravenous injection of exogenous urea. The one-compartment model with first-order elimination gave a good fit to the experimental results at times greater than 8 min after the injection.

4. Both oral and intravenous loads of alanine had dose-dependent effects on the rate of urea synthesis. There was no evidence of a limit to the maximum possible rate of urea synthesis in these experiments and the values obtained were similar to published results for different stimuli and methods of measurement.

5. The rate of synthesis increased more rapidly after intravenous loads and subjective side-effects were less severe. The intravenous administration of alanine appears to be a suitable stimulus for urea synthesis.
Outcome of surgery for obstructive jaundice is not associated with reduced levels of plasma fibronectin
Authors: Hadjis N. S. , Griffin Susan , Blumgart L. H. , Knox P.
Published: August 2015

1. Reduced levels of plasma fibronectin have been implicated in the septicaemia and/or endotoxaemia that can accompany trauma or burns.

2. Patients undergoing surgery for the relief of obstructive jaundice are also at risk of developing endotoxaemia or septicaemia. In this study, levels of plasma fibronectin were measured by immunoassay and bioassay in 16 such patients.

3. No patient had a significantly reduced level of plasma fibronectin. Even in the case of patients developing a fatal septicaemia and general system failure there was no significant decrease in circulating fibronectin.

4. It is concluded that measurement of plasma fibronectin is of no prognostic value and similarly infusion of fibronectin-rich cryoprecipitate would be of no therapeutic benefit.
The measurement of breathlessness induced in normal subjects: individual differences
Authors: Adams L. , Chronos N. , Lane R. , Guz A.
Published: August 2015

1. Normal subjects show wide variability in their sensory scaling of breathlessness for equivalent degrees of ventilatory stimulation and behave ‘characteristically’ irrespective of stimulus type.

2. Observed differences are not explained by physical characteristics, ventilatory sensitivity or pattern of breathing although there is a weak association with the degree of physical fitness.

3. Differences are seen when scaling is performed with reference to both rigidly defined extremes of breathlessness (visual analogue scaling) and a subject's own relative changes in the intensity of this sensation (magnitude estimation).

4. These findings may explain the common observation, in patients with respiratory disease, of dyspnoea out of proportion to the pathophysiological state.
Erythrocyte aldehyde dehydrogenase activity in alcoholic subjects and its value as a marker for hepatic aldehyde dehydrogenase in subjects with and without liver disease
Authors: Matthewson K. , Record C. O.
Published: August 2015

1. Erythrocyte aldehyde dehydrogenase activity was assayed in actively drinking alcoholics, patients with alcoholic liver disease who claimed to be abstaining, patients with non-alcoholic liver disorders and normal controls. Hepatic cytosolic aldehyde dehydrogenase was also assayed in the majority of the subjects.

2. Actively drinking alcoholics had significantly lower erythrocyte aldehyde dehydrogenase activity than controls (P < 0.01) but abstaining alcoholic liver disease and non-alcoholic liver disorder subjects did not.

3. There was a significant correlation between erythrocyte and hepatic cytosolic aldehyde dehydrogenase activity in the control group (r = 0.94, P < 0.05) but not in the other study groups.
Effect of low dose adrenaline and noradrenaline infusions on airway calibre in asthmatic patients
Authors: Berkin K. E. , Inglis G. C. , Ball S. G. , Thomson N. C.
Published: August 2015

1. Airway, cardiovascular and metabolic responses were measured in six asthmatic patients with stable asthma during separate adrenaline, noradrenaline and control infusions. Four incremental infusion rates (4, 10, 25 and 62.5 ng min−1 kg−1) produced circulating catecholamine concentrations within the physiological range.

2. Specific airways conductance and maximal expiratory flow rates measured from complete and partial flow-volume curves increased significantly (P < 0.05) during adrenaline infusion, in a dose-response manner.

3. No changes in specific airways conductance or maximal expiratory flow rates were seen during the noradrenaline or control infusion.

4. The highest adrenaline infusion rate caused a rise in systolic blood pressure (P < 0.05) and plasma glucose (P < 0.05) and a fall in plasma potassium (P < 0.05).

5. Noradrenaline infusion caused a slight increase in diastolic blood pressure (P < 0.05) but no metabolic changes. No cardiovascular or metabolic changes occurred during the control infusion.

6. Infused adrenaline, producing circulating concentrations within the physiological range, caused dose-related bronchodilatation in asthmatic patients. Circulating noradrenaline does not appear to have a role in the control of basal airway tone in asthmatic patients.
Ischaemic exercise test in myoadenylate deaminase deficiency and McArdle's disease: measurement of plasma adenosine, inosine and hypoxanthine
Authors: Sinkeler S. P. T. , Joosten E. M. G. , Wevers R. A. , Binkhorst R. A. , Oerlemans F. T. , van Bennekom C. A. , Coerwinkel M. M. , Oei T. L.
Published: August 2015

1. Plasma adenosine, inosine and hypoxanthine concentrations were assayed in seven control subjects, five myoadenylate deaminase deficient (MADD) patients and six McArdle patients before and after ischaemic forearm exercise.

2. The plasma adenosine increase was very low in all test groups and there were no significant differences.

3. The MADD patients showed a significantly lower increase of plasma inosine and hypoxanthine after exercise as compared with the controls.

4. In the McArdle patients the increase in plasma inosine and hypoxanthine after exercise did not differ significantly from the values measured in the controls.

5. The ischaemic exercise test with measurement of plasma inosine and hypoxanthine might be of diagnostic value in MADD, but not in McArdle's disease.
Mitochondrial damage and the subcellular distribution of 2-oxoglutarate:glyoxylate carboligase in normal human and rat liver and in the liver of a patient with primary hyperoxaluria type I
Authors: Danpure C. J. , Purkiss P. , Jennings P. R. , Watts R. W. E.
Published: August 2015

1. The subcellular distribution of 2-oxoglutarate:glyoxylate carboligase was investigated in a normal human liver, a liver from a patient with pyridoxine-resistant primary hyperoxaluria type I and rat livers subjected to various degrees and types of trauma.

2. On continuous sucrose gradients most of the carboligase fractionated with a peak equilibrium density of 1.19–1.20 g/cm3 and paralleled the distribution of the major peaks of monoamine oxidase, glutamate dehydrogenase and cytochrome oxidase and can be considered to be mitochondrial. Various proportions of the carboligase and mitochondrial marker enzymes were found to be ‘extramitochondrial’ (at or near the top of the sucrose gradients), depending on the liver source and the severity of trauma to which they were subjected.

3. Carboligase, monoamine oxidase (outer membrane marker) and glutamate dehydrogenase (matrix marker) were released from mitochondria by the homogenization and centrifugation procedures, to the extent of 19.9%, 32.4% and 11.5% respectively in hyperoxaluric liver, 12.5%, 17.9% and 8.2% in normal human liver and 3.0%, 4.9% and 3.8% in control rat liver. The proportion of extramitochondrial cytochrome oxidase (inner membrane marker) was virtually undetectable in both human and rat livers. However, sonication of rat liver homogenates or the addition of the detergent Triton X-100 caused a massive release of all four enzymes.

4. The extramitochondrial carboligase was probably in the form of a free protein of very high molecular weight or aggregate, rather than associated with a mitochondrion-derived organelle.

5. Subfractionation of a rat liver mitochondrial preparation indicated that most of the carboligase activity paralleled activities of 2-oxoglutarate decarboxylase, citrate synthase and glutamate dehydrogenase and was probably located in the matrix. The data were compatible with a previous suggestion that most of the carboligase is identical with the first decarboxylating component of the 2-oxoglutarate dehydrogenase complex. However, a significant minority of the carboligase activity showed a distribution different from that of 2-oxoglutarate decarboxylase, possibly due to structural alterations in the multi-enzyme complex.

6. We conclude that 2-oxoglutarate:glyoxylate carboligase is probably wholly mitochondrial and that the apparent cytosolic form of this enzyme is due to mitochondrial damage. Therefore previous suggestions that the lack of this component causes primary hyperoxaluria type I are no longer tenable.
Atrial natriuretic peptide inhibits the aldosterone response to angiotensin II in man
Authors: Anderson J. V. , Struthers A. D. , Payne N. N. , Slater J. D. H. , Bloom S. R.
Published: August 2015

1. We have investigated the interaction between the recently discovered natriuretic factor alpha human atrial natriuretic peptide (alpha h-ANP) and the renin-angiotensin-aldosterone system in man.

2. Angiotensin II infused with placebo produced a significant rise of plasma aldosterone concentration (mean ± sem increment 352 ± 23 pmol/l, n = 7, P < 0.001). The infusion of alpha h-ANP together with angiotensin II largely abolished the aldosterone response (P < 0.001).

3. Diastolic blood pressure rose in response to the infusion of angiotensin II with placebo (mean increment 21.0 ± 0.9 mmHg, P < 0.001). Systolic blood pressure increased to a lesser degree (mean increment 12.5 ± 0.7 mmHg, P < 0.001).

4. The infusion of alpha h-ANP together with angiotensin II significantly blunted the diastolic pressor response (P < 0.01). This ability of alpha h-ANP to blunt the pressor effect of angiotensin II may be important in the control of systemic blood pressure.

5. The inhibition of angiotensin II-stimulated aldosterone release demonstrates that alpha h-ANP may not only be a circulating natriuretic factor in its own right but that it may also act as a modulator of a related endocrine system.
Tubular reabsorption rates for myoglobin in the isolated perfused rat kidney
Authors: Ratcliffe P. J. , Esnouf M. P. , Ledingham J. G. G.
Published: August 2015

1. The renal handling of myoglobin has been studied in the isolated perfused rat kidney.

2. Myoglobin was freely filtered. Reabsorption by the renal tubules showed saturation kinetics with a relatively low maximum rate of reabsorption (Tmax) of 27-30 μg min−1 g−1 wet wt. at a perfusate concentration of 70-80 μg/ml. Myoglobin reabsorption is therefore much less than that reported for immunoglobulin light chain or lysozyme in this model.

3. Large increases in sodium and water excretion produced by omission of oncotic agent from the perfusate did not alter the kinetics of myoglobin reabsorption.

4. The use of bovine serum albumin as oncotic agent in the perfusate prevented the tubular reabsorption of myoglobin. Small amounts of albumin are filtered by the isolated perfused kidney and it is postulated that this albumin interferes with tubular reabsorption of myoglobin.
Plasma catecholamines in pregnancy induced hypertension
Authors: Rubin Peter C. , Butters Lucy , McCabe Rosemary , Reed John L.
Published: August 2015

1. Increased activity of the sympathetic nervous system has been implicated in the genesis of early hypertension in young people. Studies in pregnancy allow observations to be made on evolving, recently established and resolving hypertension in the human. We describe the results of two studies involving women who developed hypertension during pregnancy.

2. In the first study, plasma concentrations of noradrenaline and adrenaline were measured in 17 women with pregnancy induced hypertension (PIH) and 17 normotensive pregnant control subjects. Plasma noradrenaline (nmol/l) was lower in the PIH group compared with control patients in both semi-recumbent (1.11 ± 0.53 vs 1.98 ± 0.96, P < 0.001) and standing positions (1.31 ± 0.65 vs 2.57 ± 1.27, P < 0.005). Five days post partum, plasma noradrenaline had risen in the PIH group compared with pregnant values in semi-recumbent (1.65 ± 1.0 vs 1.11 ± 0.52, P < 0.05) and standing positions (2.46 ± 1.5 vs 1.31 ± 0.65, P < 0.05). In the normotensive patients plasma noradrenaline did not differ between post partum and pregnant values (1.51 ± 0.73 vs 1.98 ± 0.96 semi-recumbent; 2.00 ± 1.16 vs 2.57 ± 1.7 standing).

3. Logarithmic transformation of the noradrenaline concentration data resulted in a significant (P < 0.02) negative correlation with diastolic blood pressure in the pregnant patients but not post partum. Plasma adrenaline concentration was the same in both groups.

4. In the second study, plasma concentrations of noradrenaline and adrenaline were measured sequentially through pregnancy in five women who developed PIH and five control subjects who remained normotensive. There was no difference in catecholamine concentrations between groups at any stage, but noradrenaline concentration tended to fall as blood pressure rose in the PIH patients.

5. We conclude that the sympathetic nervous system does not contribute to the development of PIH but responds to the increased blood pressure with decreased activity.
Pressor effect of arginine vasopressin in progressive autonomic failure
Authors: Williams T. D. M. , DaCosta D. , Mathias C. J. , Bannister R. , Lightman S. L.
Published: August 2015

1. The blood pressure (BP) and heart rate (HR) responses to 5 min incremental intravenous infusions of noradrenaline (NA) and arginine vasopressin (AVP) were investigated both in patients with progressive autonomic failure (PAF) and in normal volunteers.

2. Stepwise infusion of NA at rates of 300–3000 pmol min−1 kg−1 produced a bradycardia and a dose related increase in BP in normal subjects. In subjects with PAF there was no significant HR response but the dose-BP response was shifted to the left with significant pressor responses at infusion rates of 60–300 pmol min−1 kg−1.

3. Stepwise infusion of AVP at 0.2–5.0 pmol min−1 kg−1 caused transient bradycardia but no pressor response in seven normal volunteers. Further increases in AVP infusion in three other subjects achieved plasma AVP levels as high as 3000–4000 pmol/l, and still no significant pressor response was observed.

4. Stepwise infusion of AVP at 0.05–2.0 pmol min−1 kg−1 in the eight subjects with PAF resulted in a pressor response without any change in HR. During this infusion plasma AVP increased from 0.8 ± 0.2 (mean ± se) to 30 ± 2 pmol/l. A significant pressor response was already apparent at a plasma AVP level of 5.5 ± 1.8 pmol/l.
Regulation of sodium-coupled phosphate transport by extracellular phosphate in cultured kidney cells (JTC-12)
Authors: Takuwa Yoh , Takeuchi Yasuhiro , Ogata Etsuro
Published: August 2015

1. Cultured monkey kidney cells (JTC-12) have a Na+-dependent phosphate (Pi) transport system with characteristics similar to that of the renal proximal tubule. Na+-dependent Pi uptake in JTC-12 cells is affected by Pi concentrations in the culture medium. In this investigation, further characterization of this phenomenon was carried out.

2. Lowering the concentration of extracellular Pi (3.0 mmol/l to 0.3 mmol/l) induced an increase in Na+-dependent Pi uptake compared with that in control cells maintained in 3.0 mmol/l Pi whereas Na+-dependent transport of hexose and amino acid was not altered. This response was first evident at 4 h after the extracellular Pi concentration was reduced and slowly developed over the subsequent 24 h.

3. Kinetic analysis showed an increase in the Vmax without a change in the apparent Km for Pi in cells cultured in the low Pi concentration compared with control cells.

4. The response of Pi uptake was only partially prevented by cycloheximide, suggesting that both protein synthesis-dependent and -independent mechanisms are involved in the development of the response. Insulin, which has a stimulatory effect on Pi uptake in JTC-12 cells, did not affect this response.

5. These data indicate that JTC-12 cells respond to changes in extracellular Pi concentration by changing the Na+-dependent Pi uptake system. This response has a number of properties typical of the phenomenon of adaptation of renal Pi transport in vivo to dietary phosphorus load.
Superoxide anion production and degranulation of rat neutrophils in response to acetaldehyde-altered liver cell membranes
Authors: Williams A. J. K. , Barry R. E.
Published: August 2015

1. Rat liver membrane vesicles were exposed to acetaldehyde, with or without reduction of the resultant adducts formed.

2. Superoxide anion production and degranulation of rat neutrophils, upon stimulation with the liver membrane vesicles, were measured by cytochrome c reduction before and after the addition of superoxide dismutase, and β-glucuronidase release respectively.

3. Preincubation with acetaldehyde significantly enhanced superoxide anion production by both the reduced and non-reduced membrane samples (1.7-fold and 4.4-fold, respectively).

4. Preincubation with acetaldehyde significantly enhanced degranulation (1.5-fold) of neutrophils in response to the non-reduced membranes only. The reductive process itself caused a marked increase (2.4-fold) in the ability of the membrane vesicles to stimulate degranulation.

5. Cytochalasin B, an inhibitor of phagocytosis, did not reduce degranulation, implying that it occurred as a consequence of cell surface stimulation.

6. Neutrophil superoxide anion production and lysosomal enzyme release in response to acetaldehyde-altered liver cell membranes could be an important mechanism of hepatocyte injury in alcoholic liver disease.
Insulin resistance and regulation of serum amino acid levels in myotonic dystrophy
Authors: Moxley Richard T. , Kingston William J. , Minaker Kenneth L. , Corbett Alastair J. , Rowe John W.
Published: August 2015

1. To quantify the degree of whole body insulin resistance in patients with myotonic dystrophy and to determine if these same patients display signs of a whole body decrease in the action of insulin on amino acid uptake and glucose disposal, three separate 120 min studies employing the euglycaemic insulin clamp technique (20, 80 and 200 m-units min−1 m−2) were performed on five ambulatory patients with myotonic dystrophy. The results were compared with findings obtained in identical studies in 21 normal volunteers.

2. Myotonic dystrophy patients showed a slower, less marked decline in the serum concentration of insulin sensitive amino acids (threonine, valine, leucine, isoleucine, tyrosine, phenylalanine) during all three insulin infusions compared with normals. The greatest difference occurred at the low physiological elevations of insulin produced by the 20 m-units min−1 m−2 infusion.

3. Alanine levels fell significantly below baseline in patients with myotonic dystrophy after 60 and 120 min of insulin infusion with all three rates of insulin infusion. Normal subjects had only a minimal, insignificant decline in arterialized alanine concentrations during the three different insulin infusions.

4. Creatinine adjusted rates of whole body glucose disposal were 30–40% lower in the myotonic dystrophy group at all three doses of insulin compared with the normals. This demonstrates that their insulin resistance was not due simply to a reduction in muscle mass.

5. The overall pattern of findings in these studies of patients with myotonic dystrophy indicates that there is a whole body derangement in the regulation of circulating amino acid levels by insulin as well as a marked decrease in the action of this hormone in stimulating glucose uptake by target tissues.
Stereophotogrammetry for measuring rates of cutaneous healing: A comparison with conventional techniques
Authors: Bulstrode C. J. K. , Goode A. W. , Scott P. J.
Published: August 2015

1. A portable stereocamera linked to a computer has been developed capable of taking photographs in the clinical situation.

2. The accuracy and precision of this system has been measured and compared with direct tracing and simple photography, the two systems currently in use for this type of work. It was found to have a precision of better than 2% and to be accurate to within 1% for edge length and area in models of chronic leg ulcers whose dimensions were known exactly. These results are between five and ten times better than direct tracing and simple photography measured under similar circumstances.

3. When used on patients' ulcers, stereophotogrammetry was found to have a precision of 2% for edge length and 3.4% for area, again between five and ten times more accurate than the other two systems.

4. The accuracy with which an epithelial edge can be identified with the naked eye, a possible limiting factor in any visual measuring system, was measured on fixed preparations of healing wounds on pigs. The mean error was found to be 240 μm with a confidence limit of 440 μm.

5. Finally, the rate of healing of chronic leg ulcers was measured in a clinical trial on patients. Only stereophotogrammetry had errors consistently smaller than the changes being measured in the clinical trial, making it the only system which can validly be used to study rates of healing in this model. It is also able to measure volume to within 5% and is unique in being able to do this non-invasively.
Enhancement of cardiac vagal action during ischaemia of the sino-atrial node
Authors: Potter Erica K. , McCloskey D. I. , Courtice Gillian P.
Published: August 2015

1. The effect of ischaemia of the sino-atrial node on cardiac vagal action was studied in anaesthetized dogs.

2. The cut, cardiac end of the right vagus nerve was stimulated with a standard supramaximal stimulus every 10 s. The arterial supply to the sinoatrial node was occluded for periods of 1–3 min during this intermittent vagal stimulation.

3. Vagal action on heart rate was potentiated during ischaemia of the sino-atrial node.
Autonomic nervous control of the heart rate during dynamic exercise in normal man
Authors: Maceel B. C. , Gallo L. , Marin Neto J. A. , Lima Filho E. C. , Martins L. E. B.
Published: August 2015

1. The relative contribution of the efferent components of the sympathetic and parasympathetic nervous systems to the heart rate (HR) response to dynamic physical exercise was evaluated in 23 normal males.

2. The dynamic exercise was performed on a bicycle ergometer at work loads of 25, 50 and 100 W, before and after pharmacological blockade with atropine (13 individuals) or propranolol (10 individuals).

3. Parasympathetic blockade significantly depressed the rapid HR response at the beginning of the exercise period at all levels of intensity, whereas sympathetic blockade only affected the slow-response phase (1–4 min), especially at the highest level of effort.

4. The present results suggest that the tachycardia evoked by dynamic exercise is mediated by a biphasic mechanism initially depending on rapid vagal release, which increases progressively with increasing effort. An increased sympathetic activity manifests itself in a more delayed manner, especially at the higher levels of activity.

5. Continuous monitoring of HR during the entire period of activity at different levels of intensity permits the utilization of dynamic exercise as a simple and non-invasive method for the functional evaluation of the two components of the autonomic nervous system of the heart.
Intracellular ion metabolism in erythrocytes and uraemia: The effect of different dialysis treatments
Authors: Trevisani Maurizio , De Santo Natale , Laurenzi Martin , Di Muro Michele , De Chiara Franco , Latte Maurizio , Franzese Antonietta , Iacone Roberto , Capodicasa Giuseppe , Giordano Carmelo
Published: August 2015

1. The present report focuses on some aspects of the intra-erythrocytic cation metabolism (e.g. the maximal velocity of the Na+–Li+ countertransport and Na+/K+/Cl−1 cotransport) in uraemic patients on different dialysis treatments.

2. Patients undergoing dialysis treatment [continuous ambulatory peritoneal dialysis (CAPD) or haemodialysis (HD)] overall showed higher Na+–Li+ countertransport than controls. With regard to Na+/K+/Cl−1 cotransport, CAPD patients and controls did not differ and both showed, on average, higher values than HD patients.

3. A subgroup of HD patients was studied before and after dialysis. No significant overall changes were detected as a result of the dialysis process with regard to Na+/K+/Cl−1 cotransport. Na+-Li+ countertransport was significantly reduced by dialysis and a distinctly different response to dialysis was evident according to predialysis values. Patients with high values of Na+–Li+ countertransport showed a significant reduction in this parameter while patients with normal values showed no effect. No distinct association was detected between alteration in either Na+–Li+ countertransport or Na+/K+/Cl−1 cotransport and the clinical characteristics of the patients.

4. It is concluded that uraemia and/or dialysis influences the maximal velocity of the parameters under investigation. The effect on Na+–Li+ countertransport seems to be similar for both CAPD and HD, while Na+/K+/Cl−1 cotransport is not altered in CAPD patients.
Oestrogen-induced changes in renal haemodynamics in the rat: Influence of plasma and intrarenal renin
Authors: Evans Mr J. K. , Naish P. F. , Aber G. M.
Published: August 2015

1. The effect of oestrone acetate (in total doses of 5 and 10 mg) on systemic and renal haemodynamics and the renin-angiotensin system has been studied in adult female rats.

2. The administration of 10 mg of oestrogen resulted in a significant fall in renal blood flow associated with significant rises in both renal vascular resistance and mean arterial pressure. No changes were noted in cardiac output or total peripheral resistance at either dose.

3. Whilst the higher dose of oestrogen induced a significant increase in plasma renin activity, no change was noted in animals receiving 5 mg of oestrogen. Both regimens caused significant reductions in plasma and intrarenal renin concentrations.

4. Although renal blood flow correlated with plasma renin activity in animals with a normal renal blood flow, no such correlation was noted in animals with oestrogen-induced reductions in renal blood flow.

5. The present study demonstrates that oestrogen-induced reductions in renal blood flow result from a rise in intrarenal vascular resistance which cannot be accounted for by simultaneous changes in either plasma renin activity or renal renin concentration.
Insulin action and dynamics modelled in patients taking the anabolic steroid methandienone (Dianabol)
Authors: Godsland I. F. , Shennan N. M. , Wynn V.
Published: August 2015

1. Plasma glucose and insulin concentrations were measured during oral (OGTT) and intravenous (IVGTT) glucose tolerance tests in nine patients off- and on-treatment with the anabolic steroid, methandienone (Dianabol).

2. On-treatment, the tolerance tests showed a markedly increased insulin response accompanied by impairment of glucose tolerance, characteristics normally attributed to insulin resistance. However, fasting plasma glucose (FPG) and insulin (FPI) concentrations were significantly reduced, whereas the pattern normally associated with insulin resistance is for both to be raised.

3. IVGTT glucose and insulin profiles were analysed using an algorithm derived from the minimal models of glucose and insulin dynamics originally proposed by R. Bergman and co-workers. Measures for the following parameters were thus obtained: Si, the sensitivity of glucose disposal to insulin; Sg, net insulin independent glucose disposal; ϕ1, the integral concentration of insulin delivered during the first phase of insulin secretion relative to the initial increase in glucose concentration above a model-derived threshold; ϕ2 the sensitivity of the rate of rise of insulin concentration in the second phase of insulin secretion to the concentration of glucose above a model-derived threshold; κ, the fractional clearance rate of insulin; and tl/2, the insulin half-life.

4. Si was significantly reduced on treatment by a factor of 4. Sg, ϕ1, ϕ2 and t1/2 were all significantly increased, and κ was significantly reduced. The increases in Sg and ϕ1 both showed significant correlations with the increase in weight on-treatment.

5. The reduction in FPG and FPI can be explained by the combined effects of the increase in Sg and Dianabol-induced resistance to glucagon.

6. Application of the Bergman models proved to be of value in identifying and quantifying Dianabol-induced insulin resistance. Model-derived parameters of insulin clearance and net insulin independent glucose uptake were also of use in interpreting the changes in glucose and insulin concentrations observed. However, model-derived parameters of pancreatic insulin secretion were likely to have been confounded by reduced hepatic insulin uptake associated with a state of relative insulin resistance.