bluuebunny/crossref_metadata_2025 huggingface dataset:
A study of intracellular orthophosphate concentration in human muscle and erythrocytes by 31P nuclear magnetic resonance spectroscopy and selective chemical assay
Authors: Bevington A. , Mundy K. I. , Yates A. J. P. , Kanis J. A. , Russell R. G. G. , Taylor D. J. , Rajagopalan B. , Radda G. K.
Published: August 2015

1. In order to study the relationship between extracellular and intracellular concentrations of orthophosphate (Pi), phosphorus nuclear magnetic resonance spectra were recorded, at rest, from the flexor digitorum superficialis muscle of hypophosphataemic patients with vitamin D-resistant rickets, and patients with Paget's disease of bone before and after they had been made hyperphosphataemic by treatment with the drug ethylidene-1-hydroxy-1,1-bisphosphonate. Changes in intramuscular Pi were estimated from the ratio of the areas of the Pi to adenosine 5′-triphosphate peaks. Even though the plasma Pi concentration in these patients spanned a fourfold range (0.5–2.0 mmol/l) the corresponding intramuscular Pi concentration increased by only 70%.

2. A similar effect was observed in erythrocytes, from patients with these disorders, which were incubated in autologous plasma at 37°C, under an atmosphere of O2 + CO2 (95:5, v/v). However, chloride ions, which are transported passively across the cell membrane, showed no change in distribution between cells and plasma, indicating that there was no general effect on passive anion distribution.

3. When erythrocytes from normal subjects were incubated in autologous plasma (1.0 mmol of Pi/l) and in plasma supplemented with Pi (2.3 mmol of Pi/l), the Pi concentration in the cells, at steady state, increased only from 0.57 to 0.78 mmol/l cells, suggesting that the effect was not an artifact of disease or drug therapy.

4. It is concluded that, in human skeletal myocytes and erythrocytes, the percentage change in the concentration of cytoplasmic Pi is lower than that in plasma. This implies that these cells can buffer or regulate cytoplasmic Pi when the extracellular concentration is disturbed.
Autonomic mechanisms in the heart rate response to coughing
Authors: CaRdone Claudio , Bellavere Federico , Ferri Marcello , Fedele Domenico
Published: August 2015

1. To differentiate between the possible reflex and mechanical components in the heart rate response to cough, eight healthy subjects performed a standardized cough test before and after pharmacological autonomic blockade; to test the clinical usefulness of the cough manoeuvre two groups of diabetic patients (without and with autonomic neuropathy) were compared with a group of age-matched normal subjects.

2. Because of the use of abdominal and expiratory muscles during cough, the cardioacceleratory response was compared with that induced by an intense contraction of the arm muscles (handgrip).

3. The cardioacceleratory response was completely abolished by atropine while propranolol failed to affect it. The diabetic patients with autonomic neuropathy showed a response similar to that after cholinergic blockade. The response was similar to that induced by muscular contraction for 4 s, after which it differed showing a continued cardioacceleration. The patterns of recovery were not different.

4. The cough-induced cardioacceleration is essentially reflex in nature and under cholinergic control; initially the mechanism may be partially related to the intense contraction of abdominal and expiratory muscles; later, the arterial hypotension related to the cough may contribute to the more sustained shortening of the R–R interval.

5. The cough test may be useful for the evaluation of cardiac parasympathetic integrity.
Renal ammoniagenesis following glutamine loading in intact dogs during acute metabolic acid–base perturbations
Authors: Areas Jorge , Balian Sevag , Slemmer Dianna , Belledonne Mario , Preuss Harry G.
Published: August 2015

1. Adaptation of renal ammoniagenesis during acute metabolic acidosis in intact dogs may be nonexistent or, at least, markedly less than in chronic acidosis. This contrasts to adaptation in acute respiratory acidosis, where levels similar to those attained in chronic acidosis occur within hours.

2. Accordingly, the inability to discern marked changes in acute metabolic acidosis compared with acute respiratory acidosis has been attributed to decreased glomerular filtration rate and renal blood flow seen frequently in the former.

3. In our studies, we found early changes in ammoniagenesis and glutamine metabolism during acute metabolic acidosis, but not of the magnitude seen in chronic acidosis, even considering the changes in renal blood flow (RBF) and glomerular filtration rate (GFR). Exogenous glutamine loading allowed us to discover that the qualitative changes in glutamine metabolism during acute metabolic acidosis differed from control but fell short of those seen in chronic metabolic a acidosis.

4. We also examined glutamine metabolism when renal ammoniagenic adaptation was acutely inhibited in chronically acidotic dogs. Infusing NaHCO3 into chronically acidotic dogs decreased renal ammonia production significantly (247 μmol min−1 100 ml−1 GFR vs 148 μmol min−1 100 ml−1 GFR: P < 0.001) and glutamine extraction (111.8 μmol min−1 100 ml−1 GFR vs 90.9 μmol min−1 100 ml−1 GFR: P < 0.02).

5. The qualitative changes in renal glutamine metabolism in both studies suggest that alterations in deamination of glutamate formed from glutamine are responsible, at least in part, for adaptation to acute acid–base perturbations.

6. Compared with respiratory acidosis, adaptation to metabolic acidosis is progressive and prolonged.
The potential use of lithium as a marker for the assessment of the sources of dietary salt: Cooking studies and physiological experiments in men
Authors: Sanchez-Castillo C. P. , Seidell J. , James W. P. T.
Published: August 2015

1. Lithium was investigated for its possible use as a marker for identifying the various sources of NaCl in the diet. Micromolar concentrations of lithium can be detected in various vegetables, tap water and also in urine specimens of adult volunteers. The lithium content of vegetables varied from 6.1 to 24.5 μmol of lithium/kg dry weight, with the exception of spinach and aubergines which had much higher concentrations. The excretion of the element in 24 h urine specimens ranged from 2 to 4 μmol of lithium/day.

2. Experiments were performed to assess whether both lithium and sodium would penetrate foods at the same rate during cooking. The rates of penetration into food for both elements were proportional to their concentration in the cooking water despite a sodium/lithium ratio of 50:1.

3. Physiological experiments were conducted to investigate the handling of small doses of lithium by the body. A dose of 250 μmol of lithium was chosen as optimal and given orally to healthy volunteers in either single or continuous aqueous doses of lithium carbonate. The recoveries of oral lithium in urine were 92 ± 5% (sd) and 97 ± 4 (sd) (n = 5) for single and continuous doses respectively.

4. The daily addition of 100 mmol of oral NaCl to the diet of volunteers receiving a standard dose of lithium did not affect urinary lithium excretion rates nor the final recovery of the administerd lithium.

5. These studies suggest that lithium carbonate may be a useful marker for the uptake of NaCl into cooked food; after eating lithium-enriched food the monitoring of urinary lithium output may then be used to quantify the amount of sodium derived from the specific foods.
Effects of changes in dietary sodium intake on aortic sodium pump activity in the rat
Authors: Bradlaugh Richard , Bing Robert F. , Swales John D. , Thurston Herbert
Published: August 2015

1. Aortic smooth muscle sodium efflux was studied in normal rats undergoing salt restriction or salt loading.

2. Sodium efflux rate constant was not changed by salt loading but fell significantly with salt restriction. This change was not associated with a fall in blood pressure.

3. These studies show that smooth muscle sodium transport can be influenced by dietary salt intake but do not support the concept that salt loading leads to the inhibition of the vascular smooth muscle sodium pump.
Delayed postprandial plasma bile acid response in coeliac patients with slow mouth–caecum transit
Authors: Spiller R. C. , Frost P. F. , Stewart J. S. , Bloom S. R. , Silk D. B. A.
Published: August 2015

1. Coeliac patients are known to have an expanded bile salt pool which recirculates slowly due, at least in part, to impaired gall bladder contractility. We have investigated the possibility that delayed small bowel transit of chyme and bile may also contribute to this sluggish recycling.

2. Plasma cholylglycine, total bile acids and cholecystokinin concentrations were measured after a lactulose-labelled test meal whose mouth-caecum transit time (M–C TT) was assessed by the breath hydrogen technique.

3. Overall there were no significant differences in plasma bile acid profiles between seven healthy controls and a group of 25 coeliac patients. However, when subjects were divided according to their M–C TT, the 10 with the slowest transit were found to have significant elevation of fasting levels when compared with the 10 with the fastest transit, fasting total bile acids being 3.4 ± 1.3 versus 0.7 ± 0.6 μmol/l (P < 0.02) and fasting cholylglycine being 0.43 ± 0.17 versus 0.06 ± 0.04 μmol/l (P < 0.05) respectively.

4. Peak bile acid levels did not differ significantly between subjects with fast or slow transit. However, subjects with slow transit were found to have a delay in the return of plasma bile acid levels to fasting levels so that the 4 h postprandial levels were significantly elevated when compared with those observed in the subjects with fast transit (total bile acids 3.6 ± 1.2 versus 0.19 ± 0.1 μmol/l and cholylglycine 0.70 ± 0.13 versus 0.24 ± 0.07 μmol/l respectively, both P < 0.01).

5. We conclude that M–C TT is an important variable determining the postprandial plasma bile acid response, which should be considered when comparing different disease groups in whom gut motility may differ.
The effect of a synthetic polypeptide on the renal handling of protein in man
Authors: Beetham Robert , Dawnay Anne , Cattell William
Published: August 2015

1. Haemaccel is a synthetic polymer of partially degraded gelatin and a widely used plasma volume expander.

2. The effect of a 17.5 g infusion of Haemaccel on protein excretion was investigated in four normal subjects.

3. The urinary excretion of two low molecular weight proteins, retinol-binding protein and β2-microglobulin, increased 1000- and 500-fold respectively above the values found after administration of saline as a control. The urinary excretion of albumin did not change significantly (P > 0.5).

4. In the hour after Haemaccel administration the excretion of the two low molecular weight proteins approached at least 50% of a predicted filtered load.

5. This effect of Haemaccel may be due to inhibition of proximal tubular uptake or transport of the two proteins. Absence of any effect on albumin excretion suggests alternative mechanisms for its tubular reabsorption.

6. Haemaccel may be a valuable new agent for the study of renal tubular protein metabolism.
Fractional dextran and protein clearances in glomerulonephritis and in diabetic nephropathy
Authors: Ala-Houhala I. , Pasternack A.
Published: August 2015

1. The renal clearance of dextran and protein of different molecular sizes has been measured in 42 proteinuric patients with diabetes and glomerulonephritis.

2. In both patient groups the fractional low molecular (radii 3.0–3.6 nm) dextran clearances were significantly decreased whereas the fractional high molecular (radii 5.1–7.8 nm) dextran clearances were increased as compared with the controls.

3. A porosity/charge index was constructed by calculating the ratio of fractional clearances of neutral to anionic macromolecules (θD36/θALB, θD5.1/θIgG). In diabetic patients the relation between the fractional clearances of neutral and anionic macromolecules was dependent on glomerular filtration rate.

4. It seems likely that the altered glomerular permeability in diabetic nephropathy is associated with a decrease of charge as renal function deteriorates. In glomerulonephritis the process is different and there is a high degree of variation from case to case.
A modified single breath method for estimation of cardiac output in humans at rest and during exercise
Authors: Al-Shamma Y. M. H. , Hainsworth R. , Silverton N. P.
Published: August 2015

1. This study was undertaken to determine the accuracy of a modification of a single breath method for estimation of cardiac output. The technique incorporated a single rebreathing stage followed by a prolonged expiration. Cardiac output was determined from the O2 uptake and the instantaneous changes in O2 and CO2 in the expired gas during the prolonged expiration.

2. The mean values and the random errors (determined from the differences between pairs of estimates) of cardiac outputs in normal subjects at rest and exercise were 5.42 and ± 0.60 litres/min (2 sd, 60 pairs) and 14.1 and ±1.8 litres/min (40 pairs).

3. Larger random errors were obtained in a group of cardiac patients but, except in hypoxic patients, the mean values obtained by the single breath and the direct (Fick) methods were almost identical.

4. We conclude that our modification of the single breath method is simple to use and sufficiently reliable for use in humans both at rest and during steady states of light exercise.
Plasmin: A possible physiological modulator of the human platelet adenylate cyclase system
Authors: Adnot Serge , Ferry Nicolas , Hanoune Jacques , Lacombe Marie-Use
Published: August 2015

1. Plasmin was recently reported to inhibit platelet aggregation [1]. We report here on the interaction of plasmin with the adenylate cyclase system of human platelets. Human plasmin caused a dose-and time-dependent increase in adenylate cyclase activity when added to a crude platelet membrane preparation. Both basal and prostaglandin E1-stimulated adenylate cyclase activity doubled in presence of plasmin. This stimulatory activity was shared by papain and α-chymotrypsin, but not by thrombin which displayed a slightly inhibitory effect.

2. Plasmin not only stimulated platelet adenylate cyclase activity, but also suppressed the GTP-dependent α2-adrenergic inhibition, thereby producing a five- to six-fold increased activity measured in the presence of adrenaline and GTP.

3. These effects of plasmin on the adenylate cyclase system were suppressed by the addition of the protease inhibitor leupeptin, and of soybean trypsin inhibitor, indicating that proteolysis mediated these effects.

4. We also examined the adenylate cyclase activity in membranes prepared from intact platelets incubated with increasing doses of plasmin. Incubation of platelets with plasmin concentrations as low as 0.25 mg/ml resulted in an irreversible increase in membrane adenylate cyclase activity and suppression of the adrenaline-mediated inhibition of enzyme activity.

5. These results suggest that the proteolytic stimulating effect of plasmin on the platelet adenylate cyclase system may account for the inhibition of platelet aggregation.
Decrease in human quadriceps muscle protein turnover consequent upon leg immobilization
Authors: Gibson J. N. A. , Halliday D. , Morrison W. L. , Stoward P. J. , Hornsby G. A. , Watt P. W. , Murdoch G. , Rennie M. J.
Published: August 2015

1. Quadriceps muscle protein turnover was assessed in the post-absorptive state in six men immediately after the end of unilateral leg immobilization (37 ± 4 days) in a plaster cast after tibial fracture. A primed-constant intravenous infusion of l-[1-13C]leucine was administered over 7 h. Quadriceps needle biopsies, taken bilaterally at the end of the infusion, were analysed for muscle protein leucine enrichment with 13C.

2. Quadriceps muscle protein synthetic rate, calculated from the fractional incorporation of [13C]leucine into protein compared with the average enrichment of blood α-ketoisocaproate, was 0.046 ±0.012%/h in the uninjured leg, but was only 0.034 ±0.007%/h in the quadriceps of the previously fractured leg (P > 0.05, means ± sd).

3. Muscle RNA activity (i.e. protein synthetic rate per RNA) fell from 0.27 ±0.08 μg of protein synthesized h−1 μg−1 of RNA in the control leg to 0.14 ±0.03 μg of protein synthesized h−1 μg−1 of RNA in the immobilized leg (P > 0.02).

4. Immobilization was associated with a significant atrophy of type I muscle fibres (mean diameter 69.5 ±21 μm immobilized, 81.1 ±18 μm control, P > 0.05), but no significant change occurred in type II fibre diameter. Mean quadriceps fibre volume calculated from the values for fibre diameter and percentage of each fibre type, was smaller in the injured leg by 10.6%; this value was near to the calculated difference in muscle thigh volume (calculated from thigh circumference and skin-fold thickness) which was less by 8.3%.

5. From estimated mean daily values for quadriceps protein synthetic rate (1.65 ±0.44%/day in the control legs and 1.22±0.28%/day in the injured legs) and change in fibre volume, mean daily muscle protein breakdown rates were calculated as 1.65%/ day and 1.53%/day respectively, suggesting that muscle protein breakdown was not enhanced and may have fallen.

6. The results suggest a decrease in muscle protein turnover during limb immobilization in man, with the decrement in muscle mass being due mainly to a substantial (25%) depression of muscle protein synthesis.
Lack of effect of atrial natriuretic peptide on vasopressin release
Authors: Ogawa K. , Arnolda L. F. , Woodcock E. A. , Hiwatari M. , Johnston C. I.
Published: August 2015

1. This study was designed to investigate the effects of intracerebroventricular or intravenous atrial natriuretic peptide (ANP) on plasma arginine-vasopressin (AVP) levels, plasma renin activity (PRA), blood pressure (BP) and heart rate (HR) in conscious rats.

2. No changes were observed in plasma AVP levels and PRA after intracerebroventricular injection of ANP (0.3 nmol/kg). Also no changes were found in BP and HR after intracerebroventricular ANP injection in the dose range 0.01–0.3 nmol/ kg.

3. No significant changes were observed in plasma AVP levels after the intravenous administration of ANP at 2.5 nmol/kg to hydrated rats or at 0.1 nmol/kg and 2.5 nmol/kg to dehydrated rats, although the larger dose was sufficient to cause a small fall in BP.

4. Even after 30 min intravenous infusion of ANP at 0.1 nmol min−1 kg−1, a dose sufficient to produce very high plasma ANP levels, no change in plasma AVP could be detected, although haemodynamic changes were observed.

5. Intravenous ANP injection (2.5 nmol/kg) inhibited basal renin secretion in hydrated rats and also inhibited renin secretion which had been stimulated by prior dehydration.

6. From these studies in hydrated and dehydrated rats, there was no evidence that either intracerebroventricular or intravenous ANP administration affected AVP release in vivo.
The effect of sodium intake on rabbit renal prostaglandin E2 and thromboxane A2: dissociation from the renin–angiotensin system
Authors: Attallah Ahmad A.
Published: August 2015

1. The effects of chronic alterations in dietary sodium intake on urinary prostaglandin (PG) E2 and thromboxane (TX) B2 was investigated in the rabbit.

2. Sodium restriction, over a 15-day period, reduced daily urinary PGE2 and TXB2 in concordance with urinary flow (V) and sodium excretion (UNa+V), but increased plasma renin activity (PRA) and plasma aldosterone concentration (PAC).

3. Sodium repletion, on the other hand, increased urinary PGE2 and TXB2 in proportion to the rise in V, but reduced PRA and PAC.

4. During both sodium diets PGE2 and TXB2 correlated positively with V and negatively with PRA.

5. It is concluded that chronic sodium intake produces opposite changes in the renal prostaglandin and the renin–angiotensin systems.
The iron content of finger-nails in iron deficient patients
Authors: Djaldetti M. , Djaldetti M. , Fishman P. , Hart J.
Published: August 2015

1. The content of S, Ca, Fe, Cu and Zn in the finger-nails of 17 women with iron deficiency was examined by X-ray microanalysis and compared with that of 17 healthy women.

2. The values for all these elements were similar in both groups. The distribution curve for iron was also similar in both patients and controls. There was no correlation between the iron content of the finger-nails and the serum iron or haemoglobin levels.

3. It is suggested that the iron content of the finger-nails in iron deficient patients does not reflect their iron status.
Increased collagen synthesis and cross-link formation in the skin of rats exposed to vinyl chloride monomer
Authors: Knight Kenneth R. , Gibbons Rochelle
Published: August 2015

1. Rats treated orally with vinyl chloride (30 mg/kg) daily for 2 years developed a syndrome which included thickening of the skin.

2. Analysis of the skin showed a 26% increase in collagen deposition per unit weight, and a corresponding 30% increase in the levels of glycosylated lysine and hydroxylysine. There was a significant increase in the amounts of the labile borohydride reducible cross-links, such as the intermolecular hydroxylysinonorleucine (+ 31%) and histidinomerodesmosine (+ 42%) as well as the intramolecular allysine aldol cross-links (+ 17%).

3. These results provide evidence that fibrosis of the skin is one of the pathological consequences of exposure to vinyl chloride.
Energy expenditure in non-insulin dependent diabetic subjects on metformin or sulphonylurea therapy
Authors: Leslie P. , Jung R. T. , Isles T. E. , Baty J.
Published: August 2015

1. In the management of the non-insulin dependent diabetic patient, metformin often facilitates weight loss whereas sulphonylurea may predispose to weight gain. To investigate whether this is due to alterations in energy expenditure we have studied energy expenditure in seven non-insulin dependent diabetic subjects while on metformin or sulphonylurea therapy.

2. Three components of energy expenditure were measured by indirect calorimetry, namely resting metabolic rate and the thermic responses to infused noradrenaline and to a mixed constituent meal.

3. There was no significant difference in the resting metabolic rate on metformin (5.29 ± 0.41 kJ/min; mean ± se) compared with sulphonylurea (5.34 ± 0.34 kJ/min). The resting metabolic rate was also similar to predicted values for non-diabetic subjects (r = 0.96).

4. The thermic response to infused noradrenaline was similar on metformin (23.14 ± 1.87 kJ) and sulphonylurea (21.40 ± 2.98 kJ).

5. There was no significant difference in the thermic response to the meal on sulphonylurea (75.8 ± 7.5 kJ) or on metformin (86.8 ± 10.8 kJ; 95% confidence limits − 17 to + 39 kJ).

6. We conclude that in non-insulin dependent diabetic subjects metformin does not enhance energy expenditure overall, compared with sulphonylurea.
The gut in the acute phase response: Changes in colonic and hepatic enzyme activity in response to dermal inflammation in the rat
Authors: Hutton Charles W. , Corfield Anthony P. , Clamp John R. , Dieppe Paul A.
Published: August 2015

1. Transient mild dermal inflammation was produced in rats by the subcutaneous injection of either carageenan or monosodium urate crystals. The activities of enzymes of the sialic acid metabolic pathway were measured in liver and colon at 8 h, 3 days and 7 days.

2. In both liver and colon the UDP-N-acetyl-d-glucosamine 2-epimerase and asialo-α1-acid glycoprotein sialyltransferase activities increased relative to controls while that of CMP-sialic acid hydrolase decreased. Similar changes occurred for both carageenan and monosodium urate crystals.

3. These results indicate that the acute phase response to a relatively minor inflammatory lesion causes significant changes in a distant and apparently unrelated tissue.
Acute effect of a thromboxane synthetase inhibitor on renal function in unanaesthetized sheep
Authors: Cumming Allan D. , Lindsay Robert M. , McDonald J. W. D. , Linton Adam L.
Published: August 2015

1. Eleven healthy, unanaesthetized sheep were given either a single intravenous bolus infusion of U63,577A (Upjohn), a selective thromboxane synthetase inhibitor, at a dose of 30 mg/kg (group 1, n = 6), or vehicle alone (group 2, n = 5). Animals were maintained in metabolic cages during the study, and received 150 ml of water/h and 7.5 mmol of sodium/h as Ringers lactate by intravenous infusion for 24 h before and during the study. During two 1 h control urine collections via bladder catheter, urine volume and sodium excretion closely paralleled these infusion rates.

2. In the first hour after injection of U63,577A, there were significant two- to three-fold increases in urine volume, urinary sodium excretion and fractional sodium excretion, compared with the control collections. During the subsequent 4 h, urine volume, urinary sodium excretion, and fractional sodium excretion fell to values significantly lower than in the control period. Creatinine clearance was reduced 1, 2 and 4 h post injection and returned to control values at 5 h. Urinary excretion of thromboxane B2 was significantly reduced compared with control values during the 5 h after injection of U63,577A. Excretion of 6-keto-prostaglandin F1α did not change. Plasma renin activity was significantly increased 1, 3 and 5 h after injection of U63,577A. Vehicle controls showed no change in any of the above parameters.

3. The results indicate that in healthy conscious sheep, sodium and water replete, U63,577A has a transient but significant diuretic and natriuretic effect, followed by sodium and water retention and increased plasma renin activity. The results may reflect an antidiuretic/antinatriuretic effect of thromboxane A2, or possibly diversion of cyclic endoperoxides into formation of vasodilator/natriuretic prostaglandins. These effects might be exaggerated and/or modified in conditions where arachidonic acid metabolism is stimulated.
Ventilatory responses to inhaled carbon dioxide at rest and during exercise in man
Authors: Jacobi Margaret S. , Iyawe Vincent I. , Patil Chandu P. , Cummin Andrew R. C. , Saunders Kenneth B.
Published: August 2015

1. Rapid steady-state CO2 responses were determined in six normal subjects at rest and five subjects at four different work loads up to 125 W, by injecting pure CO2 at constant flow into a small mixing chamber in the inspiratory limb of a breathing circuit.

2. The time course of the response of ventilation (V) and mean alveolar Pco2 (Paco2) was checked in separate experiments, where the flow rate of injected CO2 was changed abruptly and the effects were followed for 10 min.

3. V and Paco2 were measured every breath, and the results ensemble-averaged for each subject (two or three runs per subject) and then for the groups as a whole, in 30 s or 60 s time bins.

4. Paco2 during exercise was estimated by graphical reconstruction from the sloping alveolar plateau, and separately by the empirical equation of Jones, Robertson & Kane [1]. At rest, Paco2 was assumed equal to end-tidal Pco2 (Petco2).

5. With the constant inflow technique, 4 min was required to reach steady-state V and Paco2 during exercise, and 6 min at rest.

6. At rest, with 4 min steps (doubtful steady state) the averaged CO2 response was concave up. With 6 min steps the response was almost linear. In neither case was the deviation from linearity statistically significant.

7. During exercise, the averaged CO2 responses were essentially isocapnic at work loads greater than 75 W with either method of deriving Paco2.
Disturbance of acid–base balance in the young spontaneously hypertensive rat
Authors: Lucas P. A. , Lacour B. , McCarron D. A. , Drüeke T.
Published: August 2015

1. The acid–base status of young spontaneously hypertensive rats (SHR) was compared with that of Wistar–Kyoto rats (WKY) in the steady state, after acid loading and after blood pressure had been maintained at normal levels from weaning. Whole blood ionized calcium was measured simultaneously.

2. In the prehypertensive stage (4 weeks of age), plasma bicarbonate was significantly lower in SHR than in WKY, while blood pH did not differ significantly.

3. After 6 weeks of age, blood pH and plasma bicarbonate were significantly lower in both anaesthetized and conscious SHR than in corresponding WKY. After 7 days administration of NH4Cl in the drinking fluid, both parameters decreased significantly in both strains and the difference in pH remained constant (0.05 pH unit, P < 0.01).

4. In none of the groups investigated did non-pH-adjusted ionized calcium differ significantly between the SHR and WKY.

5. Prevention of the development of hypertension in SHR by hydralazine treatment from weaning did not increase pH or bicarbonate compared with untreated SHR, indicating that the metabolic acidosis in the SHR was not a consequence of raised blood pressure.

6. Disturbance in acid–base balance may be involved in the pathogenesis of raised blood pressure in this animal model of genetic hypertension.
Abnormal diurnal urinary sodium and water excretion in diabetic autonomic neuropathy
Authors: Bell G. M. , Reid W. , Ewing D. J. , Cumming A. D. , Watson M. L. , Doig A. , Clarke B. F.
Published: August 2015

1. Diurnal patterns of urine output and sodium and potassium excretion were studied in 10 diabetic patients with and 10 without autonomic neuropathy, and in 10 normal subjects.

2. The diurnal patterns of excretion in the diabetic patients with autonomic neuropathy differed significantly from the two other groups, as a smaller proportion of the 24 h output of urine, sodium and potassium was excreted during the day and a larger proportion was excreted at night.

3. Similar changes were noted in the diurnal patterns of urinary kallikrein excretion in diabetic patients with autonomic neuropathy, and urinary kallikrein output correlated significantly with urine volume but not with urinary sodium excretion.

4. The diurnal patterns of excretion of urinary prostaglandin E2 and 6-keto-PGF1α were not significantly different in diabetic patients with autonomic neuropathy.

5. Nocturia was a common complaint in this group, and the number of nocturnal voidings correlated with night urine volume. There was no evidence of premature bladder emptying.

6. The changes observed in the day/night urine output and sodium excretion could not be explained by glycosuria, insulin regimens, impaired renal function or abnormal diurnal prostaglandin excretion; their possible relevance to the diurnal changes of urinary kallikrein excretion is discussed.
Dissociation between plasma atrial natriuretic peptide levels and urinary sodium excretion after intravenous saline infusion in normal man
Authors: Singer Donald R. J. , Shore Angela C. , Markandu Nirmala D. , Buckley Martin G. , Sagnella Giuseppe A. , Macgregor Graham A.
Published: August 2015

1. Plasma immunoreactive atrial natriuretic peptide (ANP) and urinary sodium excretion were measured in six normal male subjects before, during and for 195 min after a 60 min infusion of 2 litres of saline (0.9% NaCl, 308 mmol of Na+).

2. During the saline infusion, there was a significant increase in plasma ANP and urinary sodium excretion and a significant decrease in plasma renin activity, aldosterone, albumin, creatinine and packed cell volume.

3. The maximal rise in mean plasma ANP occurred 15 min after stopping the infusion and the maximal rise in mean urinary sodium excretion in the collection period 30 min later.

4. Plasma ANP then decreased so that by the end of the study the level was the same as before the saline infusion. However, at this time, 195 min after the saline infusion was stopped, there was still a net positive sodium balance of 220 mmol and urinary sodium excretion remained significantly elevated.

5. Our results are compatible with the concept that increased ANP secretion may play a role in the immediate increase in sodium excretion after a saline load. However, they also suggest that other mechanisms may be more important for the longer term increase in sodium excretion.
Evidence for an inhibitor of leucocyte sodium transport in the serum of neonates
Authors: Morris J. F. , McEachern M. D. , Poston L. , Smith S. E. , Mulvany M. J. , Hilton P. J.
Published: August 2015

1. In confirmation of previous studies, serum obtained from cord blood demonstrated endogenous digoxin-like immunoreactivity (EDLI). Sera from pregnant women in the third trimester also demonstrated EDLI, which disappeared after delivery.

2. Cord serum inhibited the total sodium efflux rate constant of a mixed leucocyte preparation when compared with the effect of control serum. This inhibition resulted from a depression of the ouabain-sensitive (sodium pump) component of the rate constant.

3. An ultrafiltrate of the serum (mol. wt. < 30 000) also inhibited ouabain-sensitive leucocyte sodium transport when compared with filtrate obtained from control serum.

4. DHA-S Dehydroepiandrosterone sulphate (DHA-S) and cortisone, both present in high concentration in cord serum, demonstrated EDLI but did not affect leucocyte sodium transport in the cells of normal subjects.

5. DHA-S had no effect on sodium transport or vasoconstrictor activity in human omental resistance vessels.

6. It is concluded that EDLI of cord serum is associated with sodium transport inhibitory activity. This is unlikely to be attributable to DHA-S or cortisone.
Intravenously administered frusemide increases glomerular permeability
Authors: Ala-Houhala I. , Vapaatalo H. , Pasternack A.
Published: August 2015

1. The effects of frusemide on glomerular permeability were investigated in eight proteinuric patients by measuring the fractional protein and dextran clearances and correlating these observations with changes in renal haemodynamics.

2. Frusemide increased significantly the fractional albumin and IgG clearances. The fractional dextran clearances of molecules with a radius ≥ 5.4 run also increased significantly after frusemide injection. Pretreatment with indomethacin partly inhibited the increments in clearances of macromolecules.

3. The changes in the fractional protein clearances correlated significantly with those of inulin clearance There was also a high degree of correlation between the changes in fractional protein clearances and prostanoid excretion.

4. The data obtained suggest that frusemide increases glomerular permeability by influencing the effective pores of the glomerular capillary wall. The increased permeability possibly is due to changes in prostanoid synthesis.
Lack of effect of acute ethanol consumption on active cation fluxes of leucocytes and erythrocytes in healthy humans
Authors: Green Rachel J. , Baron D. N.
Published: August 2015

1. Acute ethanol consumption in human volunteers did not appear to alter active cation fluxes by Na+,K+-ATPase, or intracellular electrolyte concentrations, in peripheral leucocytes or erythrocytes.

2. Urinary electrolyte excretion was decreased after ethanol consumption, compared with controls.

3. Neither plasma glucose nor serum insulin was altered by ethanol.

4. After ethanol consumption there was an elevation of endogenous plasma adrenaline levels. This was accompanied by a leucocytosis, which could be attributed to a raised neutrophil count.

5. The raised adrenaline levels were not associated with hypokalaemia.

6. It is possible that in vivo ethanol may prevent adrenaline-induced hypokalaemia by fluidizing the membrane and/or decreasing the affinity of β-receptors for adrenaline.
Effects of a single moderate dose of alcohol on blood pressure, heart rate and associated metabolic and endocrine changes
Authors: Stott D. J. , Ball S. G. , Inglis G. C. , Davies D. L. , Fraser R. , Murray G. D. , McInnes G. T.
Published: August 2015

1. The effects of a single moderate dose of alcohol on blood pressure, heart rate and associated metabolic and endocrine changes were studied in 10 healthy subjects and compared with those of an isocaloric glucose control drink.

2. Systolic blood pressure rose at 1 h after both alcohol and the control drink. Therefore this early change was not specifically due to alcohol ingestion. Subsequently, there was a tendency (not statistically significant) for supine and erect systolic blood pressure to be reduced up to 8 h after alcohol ingestion. There were no consistent late changes in blood pressure observed over 7 days after alcohol.

3. Alcohol caused a marked tachycardia in both supine and erect postures which persisted beyond the time of detectable blood alcohol levels.

4. Blood sugar rose by a similar amount after alcohol and the isocaloric glucose control drink, but peak plasma insulin levels were higher after the control drink.

5. Plasma sodium rose in keeping with alcohol induced water diuresis. No significant changes in plasma potassium or magnesium were seen after alcohol.

6. Compared with the control drink there was no evidence from measurements of circulating adrenaline, noradrenaline, Cortisol, aldosterone or renin of activation of the sympathoadrenal axis, adrenal cortex or renin–angiotensin systems after alcohol.
Paradoxical inhibition of atrial natriuretic peptide release during pacing-induced hypotension
Authors: Erne P. , Raine A. E. G. , Burgisser E. , Gradel E. , Burkart F. , Buhler F. R.
Published: August 2015

1. To determine the influence of loss of atrioventricular synchrony on release of atrial natriuretic peptide (ANP), plasma ANP concentrations were measured by radioreceptor assay in 16 patients during sequential and ventricular cardiac pacing at normal heart rates.

2. Ventricular pacing induced an increase in plasma ANP concentrations (means ± SEM) from 44 ± 3 to 104 ± 4 pmol/l (P < 0.01) in 11 patients in whom systemic blood pressure was maintained.

3. In contrast, when ventricular pacing was associated with a fall in blood pressure (five patients), ANP levels (means ± SEM) fell from 68 ± 6 to 14 ± 4 pmol/l (n = 5, P < 0.05) within 5 min, despite an increase in atrial pressure. Plasma catecholamines also rose significantly in these latter patients.

4. We conclude that when loss of atrioventricular synchrony is well tolerated haemodynamically, cardiac release of ANP is increased in keeping with elevation in atrial pressure. However, the fall in plasma ANP concentration observed when ventricular pacing produces a fall in blood pressure suggests that in addition to atrial pressure, ANP release may be influenced by negative feedback mechanisms, possibly involving the baroreflex and autonomic nervous system.
Studies to assess the biological relevance of anti-Tamm–Horsfall protein antibodies detected by direct-binding enzyme-linked immunosorbent assay
Authors: Hunt J. S. , Groufsky Anne , Lynn K. L.
Published: August 2015

1. A role has been suggested for anti-Tamm–Horsfall protein (THP) antibodies in renal disease based on the results of immunoassays of pathological sera. The putative autoantibodies have not been isolated from such sera nor have definitive inhibition studies of their binding been carried out. We have carried out such studies using rabbit anti-THP antibodies as control reagents.

2. Urinary THP prepared by salt precipitation was used to prepare four immunoabsorbent columns by covalent coupling to CNBr-activated Sepharose 4B. After washing with a variety of dissociating agents to remove any non-covalently bound subunit THP, each column was incubated with normal and immune rabbit serum. Fractions washed and eluted from columns were tested for anti-THP antibodies by enzyme-linked immunosorbent assay (ELISA) and THP antigen by radioimmunoassay, and showed NH4SCN (3 mol/l) and guanidine hydrochloride (GuHCl) (6 mol/l) equivalent and sodium dodecyl sulphate (20 g/l) to be inferior in their capacity to produce immunoabsorbent THP capable of isolating specific antibodies from immune rabbit serum.

3. The column treated with GuHCl (6 mol/l) was used further in attempts to isolate putative anti-THP antibodies from five patients, who had a history of urinary tract infections and whose sera showed strong binding by ELISA.

4. Results from direct and inhibition ELISA experiments on fractions collected after washing and elution with all sera suggested that the putative human anti-THP antibodies were of very low affinity and/or directed against non-subunit THP.

5. The pathological relevance of human anti-THP antibodies measured by ELISA remains to be established.
Altered platelet lipoxygenase activity in patients with low selenium
Authors: Van Rij A. M. , Wade C. , Kirk I. , Thomson C. , Robinson M. F.
Published: August 2015

1. Arachidonic acid metabolism through the lipoxygenase pathway in platelets was investigated in 11 patients with low selenium (Se) nutritional status and compared with 14 patients with a normal Se status.

2. Plasma and whole blood Se levels, as well as plasma, whole blood and platelet glutathione peroxidase (GSHPx) activity, were measured in both groups and found to be significantly lower in the group with low Se status.

3. Studies on [14C]arachidonic acid stimulated platelets demonstrated that reduced conversion of the active metabolite 12-hydroperoxyeicosatetraenoic acid to 12-hydroxyeicosatetraenoic acid occurred in patients with low Se nutrition.

4. Changes in [14C]arachidonic acid metabolism are attributed to reduced activity of the seleno-enzyme GSHPx. The effects of other factors cannot be entirely excluded.
Haemodynamic changes in man during immersion in water at different temperatures
Authors: Weston C. F. M. , O'Hare J. P. , Evans J. M. , Corrall R. J. M.
Published: August 2015

1. Stroke volume and cardiac output were measured using the Doppler ultrasound technique in 16 normal subjects immersed to the neck in water at 33°C, 35°C, 37°C and 39°C. A standard aortic diameter was assumed and results were expressed as percentage changes from pre-immersion resting values.

2. Cardiac output rose progressively at higher temperatures, increasing by 30% at 33°C and by 121% at 39°C. At thermoneutral temperatures (33°C and 35°C) this was achieved by an increase in stroke volume of 50% despite a significant decrease in heart rate. There was a further rise in stroke volume and pulse rate at higher temperatures and a mean tachycardia of 109 ± 4 beats/min was noted at 39°C. Calculated peripheral resistance reduced progressively with increasing temperature of immersion.

3. This non-invasive and simple technique may provide a non-exercise-related cardiovascular stress test to study cardiovascular responses in a variety of pathophysiological states.
Is hypercapnia necessary for the ventilatory response to exercise in man?
Authors: Murphy K. , Stidwill R. P. , Cross Brenda A. , Leaver Kathryn D. , Anastassiades E. , Phillips M. , Guz A. , Semple S. J. G.
Published: August 2015

1. Continuous recordings of arterial pH, ventilation, airway CO2 and heart rate were made during rest and during 3–4 min periods of rhythmic leg exercise in four renal patients with arteriovenous shunts.

2. The patients were anaemic (haemoglobin 6.5–9.0 g/dl) but had a normal ventilatory response to exercise as judged by the ratio of the change in ventilation to the change in CO2 production.

3. Breath-by-breath oscillations in arterial pH disappeared for the majority of the exercise period in each patient.

4. Changes in mean arterial pH and end-tidal CO2 tension with exercise were inconsistent between subjects but consistent within a given subject. On average, mean arterial pH rose by 0.011 pH unit. Changes in end-tidal CO2 tension reflected changes in mean pHa by falling on average by 1 mmHg (0.13 kPa).

5. Hypercapnia and acidaemia were not found to be necessary for the ventilatory response to moderate exercise.
Effects of sodium loading on the renal synthesis of prostanoids in the rat
Authors: Rathaus M. , Podjarny E. , Shapira J. , Kariv N. , Bernheim J.
Published: August 2015

1. The production of prostaglandin (PG) E2, F2α and thromboxane B2 (TXB2) by isolated glomeruli, cortical tubular suspensions and medullary and papillary slices was measured in normal Long–Evans rats 4, 8 and 14 days after starting on oral Na+ load and the results were compared with those of rats on a normal Na+ intake.

2. In glomeruli, PGE2 decreased at days 4 and 8, and returned to normal at 14 days. PGF2α decreased only at day 4 and TXB2 decreased in all Na+-loaded animals. In cortical suspensions, a transient decrease of PGE2 was observed at day 4. In medullary slices, PGE2 and TXB2 decreased in all experimental periods. In contrast, in papillae, a significant increase of PGE2 was observed with Na+ loading at day 8, but PGF2α and TXB2 did not change consistently.

3. Similar changes were observed in rats with hypothalamic diabetes insipidus (DI rats) Na+ loaded for 4 days, as compared with DI rats on a normal Na+ intake.

4. The results suggest that prostanoids participate in the renal adaptation to an increased Na+ intake, and that this response is relatively independent of the presence of antidiuretic hormone.
The ratio between ankle and brachial systolic pressure in patients with sustained uncomplicated essential hypertension
Authors: Hugue Ch. J. , Safar M. E. , Aliefierakis M. Ch. , Asmar R. G. , London G. M.
Published: August 2015

1. The ratio between ankle (ASP) and brachial (BSP) systolic pressures was studied using Doppler ultrasound in 66 male subjects, 33 with sustained uncomplicated essential hypertension and 33 age-matched normal controls.

2. Based on covariance analysis, the ASP–BSP relationship was significantly different in the two populations, the ASP/BSP ratio (mean ± sem) being significantly lower in hypertensive subjects (106 ± 1 vs 132 ± 2; P < 0.001).

3. While the ASP/BSP ratio was negatively correlated with age in normal subjects, no significant correlation was observed in hypertensive subjects.

4. The diameter of the terminal abdominal aorta measured by echography was significantly greater in hypertensive subjects, while full examination with Doppler ultrasound excluded any significant arterial stenosis of the lower limbs.

5. The study suggested that, in patients with sustained uncomplicated essential hypertension, the lower ASP/BSP ratio is related to changes in arterial wave transmission.
Direct effect of α-human atrial natriuretic peptide on human vasculature in vivo and in vitro
Authors: Hughes A. , Thom S. , Goldberg P. , Martin G. , Sever P.
Published: August 2015

1. The effect of a α-human atrial natriuretic peptide (1–28) (ANP) on human vasculature was investigated in vivo and in vitro. Possible involvement of vascular dopamine receptors and the renin-angiotensin system in the response to ANP was also studied in vivo.

2. Forearm blood blow was measured by venous occlusion plethysmography. Isolated human blood vessels were studied using conventional organ bath techniques.

3. ANP (0.1–1 μg/min, intra-arterially) produced a dose-dependent increase in forearm blood flow, corresponding to a 163% increase in net forearm blood flow in the study arm. This action of ANP was not antagonized by (R)-sulpiride (100 μg/min, intra-arterially), a selective vascular dopamine receptor antagonist, or 50 mg of oral captopril, an inhibitor of angiotensin-converting enzyme.

4. ANP (1 nmol/l–1 μmol/l) produced concentration-dependent relaxation of isolated human arteries, including brachial artery, but was without effect on isolated human saphenous vein.

5. ANP produces vasodilatation in vivo and relaxes isolated human arterial smooth muscle. This action of ANP may contribute to its reported hypotensive effects in vivo.