bluuebunny/crossref_metadata_2025 huggingface dataset:
The cold face test (diving reflex) in clinical autonomic assessment: methodological considerations and repeatability of responses
Authors: Heath Martha E. , Downey John A.
Published: August 2015

1. Cold stimulus applied to the face causes bradycardia and peripheral vasoconstriction (i.e. the diving reflex), and has been suggested as a test of the autonomic pathways involved. The purpose of this study was to define standard procedures for conducting the test and analysing the responses to the cold face test, to evaluate variability in responses between subjects and within subjects when the same test is repeated, and to examine its usefulness in clinical autonomic assessment.

2. Sixteen (nine female, seven male) healthy adult (21–35 years old) subjects were used. Cold stimulus was applied with gel-filled compresses. Forehead temperature under the compress as an indication of stimulus magnitude, heap rate, blood flow in the finger, toe and calf by venous occlusion plethysmography, and systolic and diastolic blood pressure were monitored. Three protocols were carried out in which the temperature (0, 5, 10, 15°C), placement (whole face, unilateral, forehead) and duration (20, 40, 60, 120 s) of the cold compress application were varied.

3. The data indicate that 0°C compresses applied bilaterally for 40 s produced the maximum bradycardia and peripheral vasoconstriction. No subject found this test to be obnoxious, but a 120 s application was objectionable to some subjects. This cold face test resulted in 22%, 72%, 59% and 44% reductions in heart rate and blood flow to the finger, toe and calf, respectively. There was significant between-subject variability, but good consistency in responses to tests repeated in the same subject on different days, at different times of day and in different seasons.

4. Two advantages of the cold face test are: (a) it can assess sympathetic-vascular smooth muscle pathways as well as the cardiac-vagal pathway; and (b) because its afferents are independent of the stretch and pressure receptors that are stimulated in other vagal–cardiac tests (Valsalva manoeuvre and respiratory sinus arrhythmia), it can help differentiate between abnormal vagal–cardiac and abnormal transducer–afferent pathway function.
Cation transport across lymphocyte plasma membranes in euthyroid and thyrotoxic men with and without hypokalaemic periodic paralysis
Authors: Oh Vernon M. S. , Taylor Elizabeth A. , Yeo Soo-Hwa , Lee Kok-Onn
Published: August 2015

1. To study potassium transport in hypokalaemic periodic paralysis in a model of striated muscle cells, we measured specific [3H]ouabain binding (the number of sodium-potassium pumps), sodium-potassium-pump-mediated (ouabain-sensitive) 86Rb+ influx and sodium-potassium-pump-independent (ouabain-resistant) 86Rb+ influx in lymphocytes in vitro.

2. The subjects comprised euthyroid and thyrotoxic men with hypokalaemic periodic paralysis between attacks, men with uncomplicated thyrotoxicosis, and healthy men matched for age and weight.

3. Thyrotoxic patients, both with and without periodic paralysis, had significantly more lymphocyte sodium-potassium pumps than normal, and a significantly greater sodium-potassium-pump-mediated 86Rb+ influx. Antithyroid treatment corrected this defect in patients with thyrotoxic periodic paralysis. Euthyroid patients with cryptogenic periodic paralysis had significantly increased sodium-potassium-pump-mediated 86Rb+ influx, but a normal number of sodium-potassium pumps.

4. Only untreated thyrotoxic and euthyroid patients with periodic paralysis showed a significant increase in sodium-potassium-pump-independent 86Rb+ influx (5.2 ± 2.8 and 4.5 ± 1.8 respectively, vs control 2.8 ± 1.0 pmol h−1 10−6 cells; mean ± sd; P < 0.001, P < 0.005).

5. We conclude that thyrotoxicosis increases the number and activity of sodium-potassium pumps and facilitates, but is probably not necessary for, periodic paralysis. Hypokalaemic periodic paralysis is associated with an increase in sodium-potassium-pump-independent potassium influx.
Calcium-entry blockers during porcine cardiopulmonary resuscitation
Authors: von Planta Martin , Weil Max Harry , Gazmuri Raul J. , Ritz Marc A. , Rackow Eric C.
Published: August 2015

1. Calcium-entry blockers increase the intramyo-cardial pH and decrease the intramyocardial Pco2 of ischaemic canine myocardium. However, the evidence documenting improvements in myocardial acidosis and in myocardial resuscitability after administration of calcium-entry blockers during cardiac arrest is incomplete. We therefore compared the effects of verapamil (0.05 mg/kg) and diltiazem (0.075 mg/kg) with those of saline placebo in an established porcine model of cardiac arrest and cardiopulmonary resuscitation.

2. After verapamil, six of 11 animals were successfully resuscitated; after diltiazem, five of 10; and after saline placebo, six of 10. Coronary perfusion and mean aortic pressures together with end-tidal CO2 concentration during precordial compression were predictive of resuscitation, independently of the drug or placebo.

3. Coronary vein pH decreased to 6.91 ± 0.06 units (mean ± sem) with concurrent increases in Pco2 to levels exceeding 100 mmHg. Coronary vein lactate increased to a maximum of 7.5 ± 0.6 mmol/l. Coronary vein acidaemia was accompanied by decreases in intramyocardial pH to 6.64 ± 0.06 units. However, each of these differences between success and failure of resuscitation was unrelated to treatment with calcium-entry blockers.

4. Accordingly, neither verapamil nor diltiazem selectively altered coronary perfusion pressure, attenuated intramyocardial acidosis or improved resuscitability after porcine cardiac arrest and cardiopulmonary resuscitation.
A new method of analysing pulmonary quasi-static pressure-volume curves in normal subjects and in patients with chronic airflow obstruction
Authors: Gugger M. , Wraith P. K. , Sudlow M. F.
Published: August 2015

1. Exponential analysis of lung pressure-volume curves is used to deal with the non-linearity of the pressure-volume relationship. A major problem of this procedure is to define the lower volume limit for exponential curve fitting.

2. In 12 healthy subjects and 24 patients with chronic airflow obstruction, a cubic function was fitted to the quasi-static pressure-volume curves to define an inflection point.

3. The exponential function of Colebatch et al. (Colebatch, H.J.H., Ng, C.K.Y. & Nikov, N. J. Applied Physiol. 1979; 46, 387–93) was then fitted to the data for volumes above the inflection point.

4. Exponential analysis with a cubic determination of an inflection point provides an objective way to describe the elastic properties of the human lungs in vivo.
Effect of lithium on the renal actions of α-human atrial natriuretic peptide in normal man
Authors: Freestone S. , Jeffrey R. F. , Bonner C. V. , Lee M. R.
Published: August 2015

1. α-Human atrial natriuretic peptide (7.5 pmol min−1 kg−1) was infused intravenously into eight healthy men after pretreatment with lithium carbonate (750 mg) or placebo.

2. Baseline sodium excretion was significantly increased after lithium, but the natriuresis during infusion of α-human atrial natriuretic peptide was attenuated.

3. Similar decreases in plasma renin activity with infusion of α-human atrial natriuretic peptide occurred on both days.

4. Administration of lithium may be associated with pharmacological effects and further work is required to validate the use of lithium clearance as a marker of proximal renal tubular sodium handling.
Epidermal growth factor accelerates functional recovery from ischaemic acute tubular necrosis in the rat: Role of the epidermal growth factor receptor
Authors: Norman Jill , Tsau Yong-Kwei , Bacay Angelito , Fine Leon G.
Published: August 2015

1. Severe, ischaemic, acute tubular necrosis was induced in rats by bilateral occlusion of the renal arteries. The experimental group received exogenous epidermal growth factor infused directly into the renal arterial circulation. Serum creatinine concentration was measured daily for 1 week. Epidermal growth factor receptor binding was measured by autoradiography of whole kidney sections. Renal cell proliferation was measured by incorporation of [3H]thymidine into DNA.

2. Serum creatinine concentration increased after acute tubular necrosis with a peak at 48 h and remained elevated above control levels after 7 days. Binding of radiolabelled epidermal growth factor occurred in all regions of the kidney 48 h after ischaemia. Treatment with exogenous epidermal growth factor attenuated the rise in serum creatinine by 4 days after acute tubular necrosis and after 7 days serum creatinine was lower than in animals that did not receive epidermal growth factor. Infusion of epidermal growth factor also increased renal DNA synthesis.

3. The increase in epidermal growth factor binding in the kidney after acute tubular necrosis and the attenuation of the increase in serum creatinine concentration by administration of exogenous epidermal growth factor, suggest a role for epidermal growth factor in recovery from ischaemic damage. The increase in DNA synthesis in response to epidermal growth factor indicates that its effect may be due, at least in part, to accelerated tubular cell proliferation.
Intrarenal angiotensin II inhibition influences the actions of atrial natriuretic peptide
Authors: Steele T. H. , Challoner-Hue L.
Published: August 2015

1. We previously found that kidneys isolated from salt-restricted rats were refractory to atrial natriuretic peptide compared with kidneys from salt-loaded rats. Because the intrarenal tissue renin-angiotensin system may modulate renal responses to atrial natriuretic peptide, we examined the effect of dietary NaCl loading on the responses of isolated perfused kidneys from normal rats to atrial natriuretic peptide, before and after the addition of angiotensin II receptor antagonists or angiotensin I converting enzyme inhibitors to the perfusate.

2. Atrial natriuretic peptide increased the glomerular filtration rate and sodium excretion of kidneys from NaCl-loaded rats. The addition of angiotensin receptor antagonists or converting enzyme inhibitors partially reversed the increments in glomerular filtration rate but not the increments in sodium excretion, leading to an increased fractional sodium excretion. In the absence of atrial natriuretic peptide, these agents did not affect glomerular filtration or sodium excretion. Kidneys from NaCl-restricted rats did not respond to atrial natriuretic peptide or to the inhibitors and antagonists, either separately or in combination.

3. After NaCl loading, the intrarenal renin-angiotensin system may augment the glomerular response to atrial natriuretic peptide while simultaneously inhibiting the natriuretic response to atrial natriuretic peptide. However, activation of the intrarenal renin-angiotensin system is not responsible for the refractoriness of kidneys from salt-restricted rats to atrial natriuretic peptide.
Role of atrial natriuretic peptide in the increase in glomerular filtration rate induced by a protein meal
Authors: Tam S. C. , Tang L. S. , Lai C. K. , Nicholls M. G. , Swaminathan R.
Published: August 2015

1. The increase in glomerular filtration rate after a protein meal is believed to be mediated by hormonal factors. Since natriuresis is often observed after a protein meal, it was postulated that the increase in glomerular filtration rate after a protein meal might be mediated by atrial natriuretic peptide.

2. Subjects were given a low, medium or high protein meal. Fluid intake was controlled so as to avoid significant extracellular fluid volume expansion. It was found that the creatinine clearance, the urea excretion, the fractional sodium excretion and the potassium excretion were elevated in all subjects after protein meals (P <0.05). These effects were not observed in subjects given a carbohydrate control meal.

3. The plasma atrial natriuretic peptide concentrations remained unchanged in all subjects except those given a high protein meal (P <0.05). There was no significant relationship between plasma atrial natriuretic peptide concentrations and creatinine clearance before or after a protein meal.

4. The data suggest that a high protein meal induces a minor increase in plasma atrial natriuretic peptide concentration, whereas a low or medium protein meal does not. It is unlikely that the change in creatinine clearance after a protein meal can be explained by a change in plasma atrial natriuretic peptide levels.
Aspects of protein metabolism after elective surgery in patients receiving constant nutritional support
Authors: Carli F. , Webster J. , Ramachandra V. , Pearson M. , Read M. , Ford G. C. , McArthur S. , Preedy V. R. , Halliday D.
Published: August 2015

1. The present study was designed in an attempt to resolve conflicting views currently in the literature relating to the effect of surgery on various aspects of protein metabolism.

2. Sequential post-operative (2, 4 and 6 days) changes in whole-body protein turnover, forearm arteriovenous difference of plasma amino acids, glucose, lactate and free fatty acids, muscle concentration of free amino acids, RNA and protein, urinary nitrogen and 3-methylhistidine, plasma concentrations of insulin, cortisol and growth hormone, and resting metabolic rate, were measured in six patients undergoing uncomplicated elective total abdominal hysterectomy.

3. All patients received a constant daily diet, either orally or intravenously, based on 0.1 g of nitrogen/kg and an energy content of 1.1 times the resting metabolic rate for 7 days before and 6 days after surgery.

4. Whole-body protein turnover, synthesis and breakdown increased significantly 2 days after surgery (P <0.05) and returned towards pre-operative levels thereafter.

5. Forearm release of branched-chain amino acids and alanine, and efflux of glucose and lactate, were enhanced 4 days after surgery (P <0.05). Muscle glutamine and alanine concentrations were decreased on the fourth and sixth days after surgery (P <0.05). The RNA/protein ratio (indicating the capacity for protein synthesis) was unaltered.

6. A significant increase in urinary nitrogen and 3-methylhistidine was observed on days 3 and 4 after surgery (P <0.05). Thereafter, these parameters remained elevated, although failing to reach statistical significance.

7. The resting metabolic rate was significantly increased (P <0.05) 2 days after surgery but the respiratory quotient (0.77) was unchanged.

8. These data support the contention that whole-body protein synthesis and breakdown increase after surgery. Differences observed pre- and post-operatively between leucine kinetic estimates and other methods of quantifying protein metabolism indicate that only like methodologies should be compared.
Substrate Utilization during Exercise in Chronic Cardiac Failure
Authors: Riley M. , Elborn J. S. , Bell N. , Stanford C. F. , Nicholls D. P.
Published: August 2015

1. Skeletal muscle metabolism in chronic cardiac failure may be influenced by the many circulatory and neurohumoral adaptations in the condition. We investigated aerobic metabolism during exercise using indirect calorimetry in 15 patients with chronic cardiac failure and in 14 control subjects. Subjects exercised on a treadmill for 20 min at a steady-state submaximal workload.

2. Venous lactate levels were relatively constant throughout the exercise, although they were slightly greater in the patients with chronic cardiac failure than in the control subjects. The respiratory exchange ratio was lower in patients with chronic cardiac failure (0.777 ± 0.021 vs 0.833 ± 0.037, means ± sd; P < 0.0002, Mann-Whitney U-test). Relative fat utilization, expressed as a percentage of total energy expenditure, was therefore greater in patients with chronic cardiac failure (71.8 ± 7.0 vs 54.1 ± 12.3%, P < 0.0005) and this was mirrored in a lower carbohydrate utilization (24.7 ± 6.5 vs 43.3 ± 12.1%, P < 0.0002). Levels of free fatty acids, glycerol and noradrenaline were greater in patients with chronic cardiac failure.

3. We conclude that there is an increased reliance on fat, as opposed to carbohydrate, metabolism during exercise in chronic cardiac failure, and that this may relate to the elevated catecholamine and free fatty acid levels present. This may be a compensatory mechanism to preserve muscle glycogen stores, but as fat utilization is less efficient in terms of oxygen consumed, this shift may further impair exercise capacity.
Distal Lithium Reabsorption in the Sodium-Restricted Rat is Not Dependent on the Urinary Sodium to Lithium Concentration Ratio
Authors: Shalmi Michael , Petersen Jørgen S. , Thomsen Klaus , Christensen Sten
Published: August 2015

1. High fractional reabsorption of lithium occurs when rats and dogs are given a low sodium diet. This has been suggested to be due to the low tubular fluid sodium to lithium concentration ratio which arises during sodium restriction allowing transport mechanisms along the distal nephron segment to accept significant quantities of lithium instead of sodium by simple competition.

2. Clearance experiments in conscious water-loaded Wistar rats maintained on either a low sodium (6 mmol/kg) or a normal sodium (120 mmol/kg) diet were performed. The rats were infused with a solution of 120 mmol/l glucose and 10 mmol/l NaCl at a rate of 6 ml/h.

3. The median fractional excretion of lithium was 19.4% in the group with a normal sodium intake, and 2.5% in the group given a low sodium diet. The urine to plasma concentration ratio of lithium was 2.5 in the normal sodium group and 0.4 in the sodium-restricted group. The urinary sodium to lithium concentration ratio was 13 in the control group and 63 in the sodium-restricted group.

4. It is concluded that the increased fractional reabsorption of lithium initiated by a low sodium intake is not likely to be due to simple competition at distal tubular nephron sites between lithium and sodium.
Glutamine Metabolism in Skeletal Muscle of Glucocorticoid-Treated Rats
Authors: Ardawi M. Salleh M. , Jamal Yasir S.
Published: August 2015

1. The effect of dexamethasone (30 μg day−-1 100 g−-1 body weight) on the regulation of glutamine metabolism was studied in skeletal muscles of rats after 9 days of treatment.

2. Dexamethasone resulted in negative nitrogen balance, and produced increases in the plasma concentrations of alanine (23.4%) and insulin (158%) but a decrease in the plasma concentration of glutamine (28.7%).

3. Dexamethasone treatment increased the rate of glutamine production in muscle, skin and adipose tissue preparations, with muscle production accounting for over 90% of total glutamine produced by the hindlimb.

4. Blood flow and arteriovenous concentration difference measurements across the hindlimb showed an increase in the net exchange rates of glutamine (25.3%) and alanine (90.5%) in dexamethasone-treated rats compared with corresponding controls.

5. Dexamethasone treatment produced significant decreases in the concentrations of skeletal muscle glutamine (51.8%) and 2-oxoglutarate (50.8%). The concentrations of alanine (16.2%), pyruvate (45.9%), ammonia (43.3%) and inosine 5′-phosphate (141.8%) were increased.

6. The maximal activity of glutamine synthetase was increased (21–34%), but there was no change in that of glutaminase, in muscles of dexamethasone-treated rats.

7. It is concluded that glucocorticoid administration enhances the rates of release of both glutamine and alanine from skeletal muscle of rats (both in vitro and in vivo). This may be due to changes in efflux and/or increased intracellular formation of glutamine and alanine.
Three Different Methods of Inhibiting Lipolysis in Human Chyme in Vitro: Efficiency and Effect on Phase Distribution of Lipids
Authors: Fine D. R. , Zentler-Munro P. L. , Northfield T. C.
Published: August 2015

1. The efficiencies of three different methods of inhibiting fatty acid production in chyme have been evaluated. The effects of each method on the phase distribution of fatty acids after ultracentrifugation have been studied.

2. Chyme fatty acid concentrations were measured during a 4 h incubation (a) without an inhibitor, (b) after acid treatment, (c) after addition of p-bromophenyl-boronic acid and (d) after heating.

3. In a separate experiment, fresh chyme was incubated to allow equilibration of lipolysis. Aliquots were treated by each inactivation method and ultracentrifuged overnight to separate the phases. Total and micellar fatty acids and glycerides were measured.

4. In the first experiment, acid treatment completely inhibited fatty acid generation producing 4 h concentrations which were 93.4 ± 5.6% (mean ± sem) of initial values compared with 398.0 ± 54.0% (P < 0.05) for uninhibited samples. p-Bromophenylboronic acid and heating gave significant but incomplete inhibition (132.9 ± 6.6% and 166.1 ± 15.2% of initial concentrations, respectively).

5. Ultracentrifugation disclosed five phases in all except the acid-treated samples, which had four. Micellar phase fatty acid concentrations were significantly higher in the acid-treated than in the untreated samples (2.6 ± 0.7 versus 1.7 ± 0.5 mmol/l, P = 0.05), as were glyceride concentrations (1.5 ± 0.4 vs 0.6 ± 0.3 mmol/l, P = 0.05).

6. It was concluded that acid treatment was the most efficient inhibitor of fatty acid production, but it disrupted the phases. p-Bromophenylboronic acid gave significant inhibition without causing phase disruption and was therefore the most useful inhibitor overall.
Regional Haemodynamic Effects of Captopril, Enalaprilat and Lisinopril in Conscious Water-Replete and Water-Deprived Brattleboro Rats
Authors: Muller A. F. , Gardiner S. M. , Compton A. M. , Bennett T.
Published: August 2015

1. The regional haemodynamic effects of intravenous bolus doses of captopril, enalaprilat and lisinopril were assessed in conscious Brattleboro (i.e. vasopressin-deficient) rats, chronically instrumented with miniaturized pulsed Doppler probes and intravascular catheters.

2. Responses to incremental doses of each drug (spanning the median effective dose for the inhibition of the pressor response to angiotensin I) were examined in both water-replete and water-deprived states.

3. In the water-replete state, the haemodynamic profiles of captopril, enalaprilat and lisinopril were generally similar, with incremental doses causing rises in mesenteric and renal flow and, to a lesser extent, hindquarters flow. There were small tachycardias and only slight falls in mean blood pressure.

4. In the water-deprived state, the effects of all three drugs were greatly enhanced; tachycardic and hypotensive effects occurred together with increases in mesenteric, renal and hindquarters flows. However, for renal flow and renal vascular conductance the effectiveness of the drugs decreased in the order enalaprilat > captopril > lisinopril, whereas for mesenteric flow and mesenteric vascular conductance the order was captopril > enalaprilat > lisinopril.

5. Since marked haemodynamic actions were seen with doses one-tenth of the median effective dose for the inhibition of the pressor effect of angiotensin I, it is likely these effects were due to inhibition of angiotensin-converting enzyme, although not necessarily to inhibition of angiotensin II production. There were differences between the regional haemodynamic effects of the drugs at higher doses (10 × the median effective dose and 2 mg/kg), these differences supporting the proposition that in future it may be possible to design angiotensin-converting enzyme inhibitors with regionally selective haemodynamic effects.
Pineal Hyperactivity in Spontaneously Hypertensive Rats: Muscarinic Regulation of Indole Metabolism
Authors: Finocchiaro Liliana M. E. , Scheucher Angelika , Alvarez Azucena L. , Finkielman Samuel , Nahmod Victor E. , Pirola Carlos J.
Published: August 2015

1. Choline acetyltransferase activity and [3H]quinuclidinyl benzylate-binding sites were detected in the pineal gland of normotensive Wistar—Kyoto rats and of spontaneously hypertensive rats.

2. In vitro, muscarinic activation by pilocarpine increased the pineal metabolic production of hydroxyindole derivatives up to 5-hydroxytryptamine and produced a less marked stimulation of melatonin biosynthesis.

3. Electrical field stimulation of pineal gland slices caused similar metabolic effects.

4. Muscarinic blockade with atropine inhibited the effects on hydroxyindole metabolism.

5. [3H]Quinuclidinyl benzylate-binding sites, indicative of muscarinic receptors, were more numerous, and basal 5-hydroxytryptamine and melatonin levels were higher, in the pineal gland of spontaneously hypertensive rats compared with Wistar—Kyoto rats.

6. The atropine-sensitive metabolic effects of pilocarpine and electrical field stimulation on the pineal gland were increased in spontaneously hypertensive rats compared with Wistar-Kyoto rats.
Insulin Resistance after Surgery: Normalization by Insulin Treatment
Authors: Brandi L. S. , Frediani M. , Oleggini M. , Mosca F. , Cerri M. , Boni C. , Pecori N. , Buzzigoli G. , Ferrannini E.
Published: August 2015

1. Injury is known to be associated with variable degrees of tissue insensitivity to insulin. We measured insulin resistance in a group of non-obese, glucose-tolerant patients undergoing major elective surgery with an uncomplicated post-operative course.

2. Shortly after surgery, hyperglycaemia (7.3 ±0.6 versus 4.2 ± 0.3 mmol/l glucose pre-surgery, mean ± sem, P < 0.01) with normal insulin concentrations (73 ±15 versus 64 ± 18 pmol/l) suggested the presence of insulin resistance. Counter-regulatory hormones were raised, whole-body protein oxidation was doubled (P < 0.01) and energy expenditure was up by 18% (P < 0.01).

3. Insulin sensitivity was quantified by clamping plasma glucose concentrations at 5.6 mmol/l during 24 h of total parenteral nutrition (15% protein, 55% glucose and 30% fat, supplying 1.25 times the measured resting energy expenditure) with a variable infusion of exogenous insulin. After surgery, eight times more insulin was needed than before surgery (14.14±1.15 versus 1.78±0.29 pmol min−1 kg−1, P < 0.001) to maintain euglycaemia.

4. After surgery, stimulation of net carbohydrate oxidation (18.8 ±1.4 versus 17.2 ± 1.8μmol min−1 kg−1 pre-operatively, not significant), suppression of lipolysis and lipid oxidation and inhibition of ketogenesis occurred to the same extent as before surgery. Of the infused nutrients, the glucose was all oxidized, amino acids replaced endogenous protein losses (= neutral nitrogen balance) and lipids were stored. Insulin administration caused no further increment in oxygen consumption or energy expenditure.

5. We conclude that: (a) uncomplicated surgery causes severe insulin resistance, the effects of which insulin can reverse; and (b) with an energy supply only slightly in excess of demand, insulin supplementation preserves body protein and energy stores effectively.
Generation of the Membrane Attack Complex during Haemodialysis: Impact of Classical and Alternative Pathway Components
Authors: Hauser Anna-Christine , Derfler Kurt , Stockenhuber Felix , Janata Oskar , Balcke Peter
Published: August 2015

1. The generation of the plasma SC5b—9 complex (the soluble form of the membrane attack complex) during haemodialysis was studied in 29 patients together with markers of the classical (C4d fragment) and alternative (Bb fragment) pathways and the common iC3b fragment.

2. In the patients dialysed with Hemophan and Cuprophan membranes, a rapid increase in the plasma levels of SC5b—9 complex, Bb fragment and iC3b fragment occurred within 15 min of the initiation of the haemodialysis procedure. The SC5b—9 complex and the Bb fragment concentrations remained at a plateau until 120 min thereafter. The iC3b fragment level showed a continual decline.

3. The C4d fragment concentrations remained unchanged, indicating that generation of the membrane attack complex is most likely due only to activation of the alternative pathway.

4. The generation of the membrane attack complex occurred throughout the full haemodialysis period. In patients treated with Polysulfon membranes no statistically significant variation in these components was noted.

5. The study shows that the membrane attack complex may be generated during the full period of the haemodialysis session and is a stable index of biocompatibility.

6. Moreover, it seems be involved directly in haemodialysis-associated phenomena.
Aldose Reductase Messenger RNA in the Lens Epithelium in vivo: Effects of Diabetes Mellitus and Galactosaemia
Authors: Lightman Susan , Bondy Carolyn , Lightman Stafford , Kador Peter
Published: August 2015

1. Quantitative in situ hybridization histochemistry was used to examine the regulation of aldose reductase messenger RNA in the rat lens after the induction of diabetes mellitus or after feeding a 50% (w/w) galactose diet.

2. Although increased staining for aldose reductase in the lens epithelium has previously been observed by immunohistochemistry after 3 weeks of diabetes or after 7 days of galactose feeding, we have not been able to detect any increase in the amount of aldose reductase messenger RNA in these cells as compared with controls (113 ± 7%, 105 ± 9%, 100 ±7%, respectively) at these time points (P >0.05).

3. After 15 days of galactose feeding, however, there was a significant increase of 140% (± 12%) in the amount of aldose reductase messenger RNA in the lens epithelial cells as compared with controls (P = < 0.001).

4. These results demonstrate that increased availability of galactose, a high-affinity substrate for the enzyme, leads to increased aldose reductase messenger RNA, which suggests a role for aldose reductase in sugar metabolism in the lens.
Relationship between the Maximum Velocity and Sodium Affinity of the Erythrocyte Sodium Pump and its Rate Constant in Blood
Authors: Thomas T. H. , MacPhail S. , Mott V. , Wilkinson R.
Published: August 2015

1. Young and mature erythrocytes from 15 normal subjects were used to compare the sodium pump rate constant measured in whole blood with the more definitive sodium affinity constant and maximum velocity of the sodium pump measured in artificial media using sodium-loaded cells.

2. Similar values were obtained from both erythrocyte fractions for the sodium affinity constant and maximum velocity and also by using two different plots. The median error in the estimate of individual sodium affinity constants and maximum velocities from regression analysis was about 20% and the precision was not improved by combining the data points for the two erythrocyte fractions.

3. The rate constant in whole blood was closely related to the sodium affinity constant and maximum velocity of the sodium pump (r = 0.75), suggesting that it was a reasonable overall assessment of available sodium pump activity.

4. Differences in the rate constant between subjects were due to differences in both the maximum velocity and sodium affinity constant of the sodium pump so that the rate constant could not be used as a guide to the underlying sodium pump physiology.
Dose-response relationships for the effects of insulin on glucose and fat metabolism in injured patients and control subjects
Authors: Henderson Alistair A. , Frayn Keith N. , Galasko Charles S. B. , Little Roderick A.
Published: August 2015

1. Twenty-four patients were studied at around 7 days after musculoskeletal injuries in order to define the nature of the impairment of sensitivity to insulin. Insulin was infused at 6, 35, 200 or 1200 m-units min−1 m−2 for 2 h and the plasma glucose concentration was ‘clamped’ at 5 mmol/l. Forearm (uninjured) glucose extraction and blood flow were measured, and whole-body substrate oxidation and energy production rates were assessed by indirect calorimetry. The patients were compared with normal control subjects.

2. Plasma insulin concentrations during infusion were similar in patients and control subjects, showing a similar metabolic clearance of insulin. At each infusion rate, the rate of glucose infusion needed to maintain euglycaemia was less in the patients than in the control subjects. The dose-response curve for whole-body glucose infusion rate against plasma insulin concentration showed diminished sensitivity and diminished maximal response in the patients. A similar pattern was seen for forearm glucose uptake, with a marked impairment of both sensitivity to insulin and maximal responsiveness.

3. The resting metabolic rate was increased in the patients compared with the control subjects, but failed to respond to insulin infusion, so that final metabolic rates were similar in patients and control subjects. At the higher insulin infusion rates, the final rate of whole-body oxidation of carbohydrate was significantly less in the patients than in the control subjects, and that of fat was significantly greater.

4. The hormonal background to this picture of insulin resistance was not striking: the injured patients showed small elevations in plasma cortisol, glucagon and noradrenaline concentrations, but not in plasma adrenaline concentration.

5. It is concluded that the insulin resistance after injury reflects both diminished responsiveness and diminished sensitivity, affects both fat and carbohydrate metabolism, and must be explained by factors other than the usually considered ‘counter-regulatory’ hormones.
Effects of dichloroacetate and bicarbonate on haemodynamic parameters in healthy volunteers
Authors: Ludvik B. , Peer G. , Berzlanovich A. , Stifter S. , Graf H.
Published: August 2015

1. It has been shown that sodium bicarbonate has no effect or could even be detrimental in various forms of metabolic acidosis. Dichloroacetate, a stimulator of the pyruvate dehydrogenase complex, might offer an alternative treatment. The present study therefore examines the metabolic and haemodynamic effects of dichloroacetate and sodium bicarbonate in healthy volunteers.

2. On 2 different days, sodium dichloroacetate (50 mg/kg body weight) or sodium bicarbonate (1.5 mmol/kg body weight) was given intravenously as as single bolus in 10 healthy volunteers. Haemodynamic parameters were measured using a microprocessor-controlled system. Measurements were performed before and 30 and 60 min after infusion.

3. After administration of dichloroacetate, cardiac index increased from 2.3 ± 0.03 to 2.7 ± 0.1 1 min−1 m−2 (P <0.05), peripheral vascular resistance decreased from 266 ± 9.7 to 240 ± 1.7 kPa s l−1 (2662 ± 97 to 2398 ± 169 dyn s cm−5, P <0.05), oxygen availability increased from 442 ± 16 to 535 ± 30 ml min−1 m−2 (P <0.05) and serum lactate concentration fell from 1.4 ± 0.14 to 0.6 ± 0.1 mmol/l (P <0.05). With infusion of sodium bicarbonate there were no significant effects on any of these variables.

4. Our results show that dichloroacetate administered intravenously reduces the serum lactate concentration. The main effects of dichloroacetate itself are on the haemodynamic variables. Dichloroacetate increases cardiac index and oxygen availability and decreases peripheral vascular resistance, whereas sodium bicarbonate has no effect on haemodynamic or metabolic parameters. These data give some further insights in the actions of dichloroacetate and support the use of dichloroacetate as alternative therapy in various forms of metabolic acidosis.
Lymphocytotoxins in sera from highly sensitized multiparous dialysis patients: antibody class, relationship with the HLA and with paternal antigens
Authors: Propper D. J. , Leheny W. A. , Urbaniak S. J. , Catto G. R. D. , MacLeod A. M.
Published: August 2015

1. Sera from 11 highly sensitized multiparous dialysis patients were studied in order to define the target antigens, antibody class and relationship with paternal HLA class I antigens of the underlying lymphocytotoxic antibodies. All sera contained lymphocytotoxic antibodies to over 70% of a panel of lymphocytes from 24 donors (panel reactivity > 70%).

2. Inhibition of cytotoxic activity against paternal lymphocytes by monoclonal antibodies to HLA framework determinants indicated that all 11 sera contained lymphocytotoxic antibodies to paternal class I antigens. In addition, five sera contained lymphocytotoxic antibodies to paternal class II antigens.

3. In order to determine the extent to which lymphocytotoxic antibodies were directed to paternal antigens, the panel reactivity of sera was compared before and after absorption with paternal peripheral blood lymphocytes. Over 50% of panel reactivity was absorbed from eight out of 11 sera, and in three of these 11 over 80% was absorbed. In the majority of patients this change in panel reactivity could be ascribed to binding of lymphocytotoxic antibodies to specific paternal class I antigens.

4. Digestion of sera with dithiothreitol had no significant effect on panel reactivity, indicating that the lymphocytotoxic antibodies were of immunoglobulin G class.

5. No sera reacted with either autologous lymphocytes or K562 cells, indicating an absence of autoantibodies.

6. These studies imply that panel-reactive lymphocytotoxic antibodies in the sera of highly sensitized multiparous patients are those which mediate hyperacute renal allograft rejection. Their development may be related to secondary humoral responses to angtigens in blood transfusions from donors who share paternal class I specificities.
Differential effects of atrial natriuretic peptide and dopamine on urinary protein excretion in chronic glomerulonephritis
Authors: Hirata Yasunobu , Ishii Masao , Fukui Kazushige , Hayakawa Hiroshi , Suzuki Etsu , Sugimoto Tokuichiro , Kimura Kenjiro , Matsuoka Hiroaki , Sugimoto Tsuneaki
Published: August 2015

1. To examine whether or not atrial natriuretic peptide-induced proteinuria simply results from increases in urine flow or glomerular filtration rate, we infused dopamine (1 μg min−1 kg−1) and α-human atrial natriuretic peptide (0.025 μg min−1 kg−1) into nine patients with chronic glomerulonephritis and nine essential hypertensive patients without renal damage, and compared the effects of the two agents on renal function and urinary protein excretion.

2. In patients with chronic glomerulonephritis, dopamine infusion significantly increased urinary sodium excretion (+ 59%), renal blood flow (+ 20%) and creatinine clearance (+ 14%). However, urinary protein excretion was not changed. Addition of atrial natriuretic peptide to the dopamine infusion further increased urinary sodium excretion and maintained creatinine clearance at the same level. In contrast to the infusion of dopamine alone, atrial natriuretic peptide markedly increased urinary protein excretion (77 versus 229 mg min−1 m2, P < 0.02). Furthermore, the addition of atrial natriuretic peptide elevated the urinary protein/creatinine ratio (1.55 versus 5.35, P < 0.05), while dopamine alone did not(1.55 versus 1.45, not significant).

3. In essential hypertensive patients, dopamine and dopamine plus ANP showed renal effects similar to those of chronic glomerulonephritis; however, the urinary excretion of protein was not changed significantly.

4. These results suggest that atrial natriuretic peptide may increase urinary protein excretion mainly by increasing the permeability of the damaged glomeruli to protein rather than by simply increasing urine flow or glomerular filtration. Possible mechanisms underlying the proteinuria-increasing effects of atrial natriuretic peptide are discussed.
Fasting Plasma Glucose Levels and Endogenous Androgens in Non-Diabetic Postmenopausal Women
Authors: Khaw Kay-Tee , Barrett-Connor Elizabeth
Published: August 2015

1. The clinical association between glucose intolerance, hyperinsulinaemia, insulin resistance and hyperandrogenism is well recognized in premenopausal women with polycystic ovarian disease. We examined the hypothesis that fasting plasma glucose levels might be related to endogenous androgen levels in postmenopausal women in the absence of overt clinical disease.

2. In a Southern Californian cohort of 848 non-diabetic postmenopausal women aged 50–79 years, fasting plasma glucose levels positively correlated with levels of the endogenous androgens dehydroepiandrosterone sulphate and free testosterone and negatively with sex-hormone-binding globulin across the whole range of glucose and hormone levels. Mean dihydroepiandro-sterone sulphate and free testosterone levels were 16% and 46% higher, respectively, and mean sex-hormone-binding globulin levels 27% lower in the top compared with the bottom quartile of fasting plasma glucose levels. This relationship was independent of age, body mass index, cigarette smoking habit and exogenous oestrogen use.

3. These findings raise questions about the possible physiological role of androgens in the regulation of glucose metabolism and insulin resistance and, possibly, in the mediation of the some of the cardiovascular consequences of diabetes in women.
Hepatic Phosphofructokinase-1 Activity and Fructose 2,6-Bisphosphate Levels in Patients with Abdominal Sepsis
Authors: Arnold Jeff , Hamer Marcus J. , Irving Miles
Published: August 2015

1. In sepsis various processes of carbohydrate metabolism, such as hepatic gluconeogenesis and glycolysis, are altered. Phosphofructokinase-1, a key glycolytic enzyme, is controlled in the long term via regulation of synthesis and degradation of the protein itself, while in the short term it is regulated by allosteric effectors, such as fructose 2,6-bisphosphate (the most potent). In the present study hepatic phosphofructokinase-1 activity as well as phosphofructokinase-2 activity and the concentration of fructose 2,6-bisphosphate were assayed to determine if they might contribute to the derangement of carbohydrate metabolism seen commonly in sepsis.

2. The levels of glycogen and fructose 2,6-bisphosphate and the activity of phosphofructokinase-1 and phosphofructokinase-2 were determined in hepatic biopsies obtained at laparotomy from six patients with and seven patients without abdominal septic foci.

3. A significant increase in plasma lactate concentration was observed in the septic patients, whereas no significant differences in tissue glycogen content or plasma glucose concentration were seen between the groups.

4. No significant change in plasma insulin concentration was observed. However, levels of the counter-regulatory hormones (glucagon, cortisol and adrenaline) were elevated in the septic patients.

5. A 60% decrease in hepatic phosphofructokinase-1 activity was seen in the septic patients. However, no significant changes in hepatic phosphofructokinase-2 activity and fructose 2,6-bisphosphate content were observed in the septic patients.

6. The present results demonstrate that the decrease in hepatic phosphofructokinase-1 activity occurring in sepsis does not appear to reflect alterations in the concentration of fructose 2,6-bisphosphate.
Skeletal muscle degradation and nitrogen wasting in rats with chronic metabolic acidosis
Authors: Williams Bryan , Layward Ellis , Walls John
Published: August 2015

1. Chronic metabolic acidosis is associated with impaired growth and negative nitrogen balance, suggesting that it promotes endogenous protein catabolism.

2. Skeletal muscle is the major repository of body protein and is a potential target for stimuli of protein catabolism.

3. This study in vivo examines the effects of chronic metabolic acidosis on the relationship between growth, nitrogen disposal and skeletal muscle catabolism in the rat.

4. Growth, nitrogen utilization and acquisition of body mass were significantly impaired in acidotic animals compared with pair-fed controls.

5. Total nitrogen excretion was significantly increased in acidotic rats despite decreased urea production. The time course of this response to acidosis was synchronous with that of accelerated protein catabolism in skeletal muscle.

6. It is proposed that metabolic acidosis impairs growth by stimulating skeletal muscle protein catabolism. It is suggested that this forms part of a co-ordinated multi-organ homoeostatic response to acidosis, skeletal muscle and down-regulated urea production supplying the nitrogen required for renal ammoniagenesis.
Effect of destruction of the vascular endothelium upon pressure/flow relations and endothelium-dependent vasodilatation in resistance beds of spontaneously hypertensive rats
Authors: Randall Michael D. , Thomas G. Roger , Hiley C. Robin
Published: August 2015

1. Pressure/flow relationships were determined in the in situ blood-perfused superior mesenteric and hindquarters vascular beds of spontaneously hypertensive rats and Wistar-Kyoto normotensive rats before and after destruction of the endothelium with detergent. The effects of indomethacin on the regression of pressure on flow were also investigated in the spontaneously hypertensive rats, as were the endothelium-dependent relaxations in response to carbachol in the mesenteric bed.

2. In the spontaneously hypertensive rats the regression line of pressure on flow in the two vascular beds was both steeper and more elevated than in the Wistar-Kyoto rats, showing that there was greater resistance to flow in the hypertensive animals. Destruction of the endothelium significantly increased the slope of the regression in both Wistar-Kyoto and spontaneously hypertensive rats: the increases in the Wistar-Kyoto rats were 2.4 ± 0.3 fold (mesenteric) and 2.0 ± 0.5 fold (hindquarters) which were comparable with the respective increases of 1.6 ± 0.3 fold and 1.8 ± 0.3 fold in the spontaneously hypertensive rats.

3. Indomethacin (5 mg/kg, intravenously) had no effect on the pressure/flow relations in either of the vascular beds of the spontaneously hypertensive rats.

4. The dose-response curves for the endothelium-dependent vasodilatation in response to carbachol were not significantly different in spontaneously hypertensive and Wistar-Kyoto rats.

5. The results suggest that tonic release of endothelium-derived relaxing factor has similar effects in modulating resistance vessel tone in vivo in both hypertensive and normotensive rats. Further, endothelium-dependent vasodilatation does not appear to be impaired in the mesenteric vasculature in spontaneously hypertensive rats, and there appears to be no significant modulation of mesenteric vascular resistance by tonic release of cyclo-oxygenase products in spontaneously hypertensive rats.
Deglycosylation of α1-proteinase inhibitor is impaired in the faeces of patients with active inflammatory bowel disease (Crohn's disease)
Authors: Mizon Charlotte , Yamani Jamal El , Colombel Jean-Frédéric , Maes Pierrette , Balduyck Malika , Laine Anne , Cortot Antoine , Tartar André , Mizon Jacques
Published: August 2015

1. α1-Proteinase inhibitor (α1-antitrypsin) was excreted in the faeces of patients with inflammatory bowel disease in different molecular forms: Mr-51 000 and Mr-45 000 forms were widely found in the stools of patients with active disease, whereas a Mr-38 000 species was frequently recovered from healthy subjects and patients with quiescent disease (Mizon, Becuwe, Balduyck et al. Clin. Chem. 1988; 34, 2268–70).

2. N-Terminal sequencing of the Mr-38000 form of α1-proteinase inhibitor, after SDS/PAGE and electro-transfer on polyvinyl difluoride membranes, showed that it differed from plasma α1-proteinase inhibitor by the loss of 17 N-terminal amino acids.

3. Carbohydrate analysis of the isolated Mr-38 000 form revealed a total lack of neutral sugars.

4. In contrast, the Mr-51000 form of α1-proteinase inhibitor is glycosylated and thus could be differentiated by virtue of its reactivity with concanavalin A. The analysis of 25 faecal extracts from patients with Crohn's disease allowed us to confirm that the presence of the glycosylated form of α1-proteinase inhibitor was closely related to the degree of inflammation.

5. From these data, it may be hypothesized that the hydrolytic activity of some glycosidases is greatly reduced in active Crohn's disease.