bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cardiac Secretion and Renal Clearance of Atrial Natriuretic Peptide in Normal Man: Effect of Salt Restriction
Authors: Sudhir Krishnankutty , Friberg Peter , Meredith Ian T. , Woods Robyn L. , Esler Murray D. , Jennings Garry L. 
Published: August 2015

1. Previous studies of endogenous atrial natriuretic peptide (ANP) in humans have examined changes in plasma levels, rather than regional secretion and clearance of the peptide. Using arterial and selective venous catheterization and sampling, and measurement of regional organ flow, we measured haemodynamics, cardiac secretion of ANP and renal clearance of ANP in six healthy volunteers at rest, on a normal sodium diet
2. Salt restriction decreases plasma concentrations of ANP. We assessed the contribution of the heart and kidney to this decrease, by measuring cardiac secretion and renal clearance of ANP at the termination of a low salt diet
3. Twenty-four hour urinary sodium excretion fell on the low salt diet from 163 to 29 mmol/day [standard error of the difference (sed) ± 14, P &lt; 0.001]. Body weight decreased on salt restriction from 76.4 to 75.4 kg (sed ± 0.33, P &lt; 0.05). Brachial mean arterial pressure fell by 6% (P &lt; 0.05), but right atrial pressure was unchanged. Renal vein plasma renin activity increased by 56% with sodium restriction (P &lt; 0.01), whereas arterial ANP concentrations fell by 39% (P &lt; 0.05)
4. Coronary sinus ANP levels fell from 417 to 268 pg/ml (sed ± 74, P &lt; 0.05), whereas renal vein concentrations were unaltered. There was a 47% decrease in cardiac secretion of ANP in the low salt state (P &lt; 0.05). Net extraction of ANP across the kidney (about two-thirds) and renal clearance of ANP were unchanged on the low salt diet. Thus decreased plasma ANP with sodium restriction is due to reduced cardiac secretion.
Clinical Science in the 1990s
Authors: Brown M. J. 
Published: August 2015

From this issue, Clinical Science will increase its page numbers from an average of 112 to 128 per monthly issue. This welcome change — equivalent to at least two manuscripts — has been ‘forced’ on us by the increasing pressure on space; this has led to an undesirable increase in the delay between acceptance and publication, and to a fall in the proportion of submitted manuscripts we have been able to accept. The change in page numbers will instead permit us now to return to our exceptionally short interval between acceptance and publication of 3–4 months; and at the same time we shall be able not only to accept (as now) those papers requiring little or no revision, but also to offer hope to some of those papers which have raised our interest but come to grief in review because of a major but remediable problem. Our view, doubtless unoriginal, has been that the review process, which is unusually thorough for Clinical Science, involving a specialist editor and two external referees, is most constructive when it helps the evolution of a good paper from an interesting piece of research.
Traditionally, the papers in Clinical Science have represented some areas of research more than others. However, this has reflected entirely the pattern of papers submitted to us, rather than any selective interest of the Editorial Board, which numbers up to 35 scientists covering most areas of medical research. Arguably, after the explosion during the last decade of specialist journals, the general journal can look forward to a renaissance in the 1990s, as scientists in apparently different specialities discover that they are interested in the same substances, asking similar questions and developing techniques of mutual benefit to answer these questions. This situation arises from the trend, even among clinical scientists, to recognize the power of research based at the cellular and molecular level to achieve real progress, and at this level the concept of organ-based specialism breaks down. It is perhaps ironic that this journal, for a short while at the end of the 1970s, adopted — and then discarded — the name of Clinical Science and Molecular Medicine, since this title perfectly represents the direction in which clinical science, and therefore Clinical Science, is now progressing.
Acetylation of 5-aminosalicylic acid by isolated human colonic epithelial cells
Authors: Ireland A. , Priddle J. D. , Jewell D. P. 
Published: August 2015

1. This study investigates the acetylation of 5′-aminosalicylic acid by isolated human colonic epithelial cells.
2. After incubation of intact cells with 0.1 mmol/l 5-aminosalicylic acid, N-acetyl-5-aminosalicylic acid was detected in a concentration of 141 (± 23.8 sem) nmol/g dry weight in the incubation medium, and 34.8 (± 5.5 sem) nmol/g dry weight intracellularly. No unchanged 5-aminosalicylic acid was detected inside the cell.
3. Acetylation of 5-aminosalicylic acid by a cell homogenate was very poor, but the addition of 1 mmol/l acetyl-CoA resulted in complete conversion of 0.1 mmol/l 5-aminosalicylic acid to N-acetyl-5-aminosalicylic acid.
4. N-Acetyltransferase activity was detected in the cytosol, with a mean of 3.3 nmol min−1 mg−1 of protein. There was no N-acetyltransferase activity in the brush border. There was no difference in enzyme activity between epithelial cells derived from normal, Crohn's disease or ulcerative colitis patients.
5. Preliminary characterization of the N-acetyltransferase enzyme suggests a molecular weight of 150 000.
Response to dynamic exercise in cardiac transplant recipients: implications for control of the sodium regulatory hormone atrial natriuretic peptide
Authors: Singer D. R. J. , Banner N. R. , Cox A. , Patel N. , Burdon M. , Buckley M. G. , MacGregor G. A. , Yacoub M. H. 
Published: August 2015

1. To study the importance of cardiac innervation in the regulation of atrial natriuretic peptide, plasma atrial natriuretic peptide levels were measured during symptom-limited, graded exercise on a cycle ergometer in seven male orthotopic cardiac transplant recipients.
2. Resting plasma atrial natriuretic peptide was significantly higher in the transplant recipients than in two control groups, one matched to the transplant recipients (group 1) and the other to the age of the donor heart (group II).
3. The response to exercise of the cardiac transplant recipients was compared with the response of control group II. Mean maximal work load achieved with exercise was around 40% lower in the cardiac transplant recipients. During exercise, plasma atrial natriuretic peptide levels increased in both the cardiac transplant recipients and the control subjects. The increase in plasma atrial natriuretic peptide with exercise was greater in absolute, but less in percentage, terms in transplant recipients than in the control subjects.
4. The increase in mean arterial pressure with exercise was similar in patients and in control subjects; however, heart rate increased in the patients by only 33% compared with a rise of 151% in the control group.
5. These results provide insight into the control of the sodium regulatory hormone atrial natriuretic peptide. First, factors other than a change in heart rate appear of importance in the regulation of atrial natriuretic peptide. Secondly, these findings suggest that cardiac innervation is not of dominant importance in the modulation of atrial natriuretic peptide secretion.
Effect of a kinin antagonist on renal function and haemodynamics during alterations in sodium balance in conscious normotensive rats
Authors: Madeddu Paolo , Glorioso Nicola , Soro Aldo , Manunta Paolo , Troffa Chiara , Tonolo Giancarlo , Melis Maria Grazia , Pazzola Antonio 
Published: August 2015

1. To evaluate whether sodium intake can modulate the action of endogenous kinins on renal function and haemodynamics, a receptor antagonist of bradykinin was infused in conscious normotensive rats maintained on either a normal or a low sodium diet.
2. The antagonist inhibited the hypotensive effect of exogenously administered bradykinin. It did not change the vasodepressor effect of acetylcholine, dopamine or prostaglandin E2.
3. The antagonist did not affect mean blood pressure, glomerular filtration rate, renal blood flow or urinary sodium excretion, in rats on sodium restriction. It did not change mean blood pressure, glomerular filtration rate or urinary sodium excretion, but decreased renal blood flow, in rats on a normal sodium intake.
4. The kallikrein–kinin system has a role in the regulation of renal blood flow in rats on a normal sodium diet.
Mucolysis of the colonic mucus barrier by faecal proteinases: Inhibition by interacting polyacrylate
Authors: Hutton D. A. , Pearson J. P. , Allen A. , Foster S. N. E. 
Published: August 2015

1. Mucolytic (mucus solubilizing) activity in human faeces has been characterized with both purified human and pig colonic mucin and shown to be mediated by proteolysis.
2. Mucolytic activity was demonstrated by: (i) a drop in mucin viscosity; (ii) a substantial reduction in mucin size, from polymer to degraded subunit, as assessed by Sepharose CL-2B gel filtration; (iii) formation of new N-terminal peptides.
3. Mucolytic activity was also followed in faecal extracts by its proteolytic activity using standard succinyl albumin substrate. Proteolysis extended over the pH range 4.5–11.0. Proteolysis was inhibited at pH 7.5 by soybean trypsin inhibitor and phenylmethanesulphonyl fluoride, suggesting the presence of serine proteinases.
4. The polyacrylate carbomer (934P) inhibited both mucolysis of pig colonic mucin and proteolysis of succinyl albumin.
5. Interaction between the polyacrylate (carbomer 934P) and purified human and pig colonic mucin was demonstrated by a marked synergistic increase in solution viscosity (360% above control).
6. The results demonstrate the presence of a mucolytic activity in the human colonic lumen that has the potential to degrade the mucus barrier, and that polyacrylates inhibit this mucolysis and interact to strengthen the colonic mucus barrier. Polyacrylates may therefore have therapeutic potential in inflammatory bowel disease where luminal proteolytic activity can be raised.
Lack of effect of an inspiratory threshold load on plasma atrial natriuretic peptide levels
Authors: Warley A. R. H. , Fontes F. , Wilson M. , Raine A. E. G. , Stradling J. R. 
Published: August 2015

1. After a run-in period, six healthy, recumbent, water-loaded male subjects breathed through an inspiratory threshold load for 90 min. To correct for prolonged recumbency, a similar protocol was followed on a separate control day, but without an inspiratory load.
2. A negative intrathoracic pressure of at least 30 cmH2O was required to overcome the threshold load.
3. Urine was collected every 30 min and analysed for sodium concentration.
4. Plasma samples were collected every 30 min and analysed for atrial natriuretic peptide concentration.
5. The inspiratory load had no effect on urine volume, urinary sodium excretion or plasma atrial natriuretic peptide levels.
Detection of osteomalacia in British Asians: A comparison of clinical score with biochemical measurements
Authors: Nisbet J. A. , Eastwood J. B. , Colston K. W. , Ang L. , Flanagan A. M. , Chambers T. J. , Maxwell J. D. 
Published: August 2015

1. In a prospective study of 160 Asian outpatients, plasma calcium, phosphate, alkaline phosphatase, 25-hydroxyvitamin D and parathyroid hormone were compared with a clinical score to determine which measurements singly or in combination were most useful in the detection of osteomalacia.
2. Bone biopsies were performed in 45 of 48 patients considered to be at risk of osteomalacia. Of the 39 quantifiable bone biopsies, nine showed unequivocal osteomalacia, 13 were judged to be borderline and 17 biopsies were normal.
3. The clinical score was highly sensitive, identifying eight of nine patients with osteomalacia, but not specific, six of 17 normal patients having an abnormal score.
4. Plasma parathyroid hormone was the best single biochemical test for identifying osteomalacia. By using a discriminant function based on parathyroid hormone and alkaline phosphatase, it was possible to classify 96% cases correctly; a discriminant function utilizing calcium, phosphate and alkaline phosphatase was successful in 85% of cases. It was not possible to discriminate between histological groups on the basis of plasma 25-hydroxyvitamin D values.
5. We confirm that the clinical score is a useful and inexpensive screening test for osteomalacia in British Asians. In those patients with an abnormal score we suggest that parathyroid hormone and alkaline phosphatase are measured. Where both parathyroid hormone and alkaline phosphatase are high, in the absence of hypercalcaemia, histological osteomalacia is extremely likely.
Bradykinin has no acute effect on the response of forearm blood flow to sympathetic stimulation in man
Authors: Cullen M. J. , Cockcroft J. R. , Webb D. J. 
Published: August 2015

1. Six healthy male subjects received 0.9% (w/v) NaCl (saline) followed by incremental doses of bradykinin (1, 3 and 10 pmol/min), via the left brachial artery. Blood flow and the response of blood flow to lower-body negative pressure were measured in both forearms during infusion of saline and each dose of bradykinin.
2. Bradykinin produced a moderate and dose-dependent increase in blood flow in the infused, but not the non-infused, forearm. Lower-body negative pressure produced an approximately 15–20% reduction in blood flow in both forearms, and this response was unaffected by local infusion of bradykinin.
3. Bradykinin, in contrast to angiotensin II, had no acute effect on peripheral sympathetic responses to lower-body negative pressure. We conclude that, in forearm resistance vessels in man, withdrawal of angiotensin II, rather than accumulation of bradykinin, is likely to account for the attenuation of peripheral sympathetic responses after acute administration of a converting-enzyme inhibitor.
Influences of propranolol and atenolol on the circadian rhythm of heart rate in elderly patients with essential hypertension
Authors: Shimamoto Hiroyuki , Shimamoto Yoriko , Sakata Shogo 
Published: August 2015

1. The influence of long-acting propranolol and of atenolol on the circadian rhythm of heart rate was assessed using 24 h electrocardiographic recordings in elderly patients with essential hypertension. Eighteen elderly patients were investigated before treatment and after 12 weeks on 60 mg of long-acting propranolol once a day; 21 elderly patients were studied before treatment and after 12 weeks on 50 mg of atenolol once a day. The mean hourly heart rate in 24 h electrocardiographic recordings was used to fit cosine curves by the statistical technique of least squares, and the following parameters were estimated: mesor (rhythm-adjusted mean of the heart rate), amplitude (one-half of the total diurnal variation of the heart rate) and acrophase (the time when the heart rate was at its peak above the mean).
2. The cosine curves were fitted with a P value of 0.01 or less before and after treatment in all patients.
3. In the long-acting propranolol group, the mesor and amplitude were reduced significantly after treatment. The acrophase appeared significantly earlier after treatment than before treatment.
4. In the atenolol group, the mesor and amplitude decreased significantly after treatment. However, the acrophase did not change with treatment.
5. We conclude that both propranolol and atenolol decrease the mesor and amplitude through blocking cardiac β1-receptors, and that only propranolol may have some effects on the central nervous system, resulting in the circadian phase shift.
Airway β-adrenoceptor number in cystic fibrosis and asthma
Authors: Sharma Rajiev K. , Jeffery Peter K. 
Published: August 2015

1. Maximal binding capacity (Bmax.) and the dissociation constant (KD) for the β-adrenoceptor antagonist 125I-cyanopindol were estimated in membrane preparations of hilar, lobar/main bronchi (level 1) and peripheral lung (level 11) of grossly normal lungs resected for bronchial carcinoma. The tissue distribution of 125I-cyanopindol-binding sites was assessed by autoradiography of complementary cryostat sections. The data obtained from the resections for carcinoma and bronchiectasis were used as disease controls for comparison with those obtained from patients with cystic fibrosis and asthma.
2. In carcinoma controls, mean Bmax. values (± sem) for airway levels 1 and 11 were 89 ± 4 and 133 ± 6 fmol/mg of protein, respectively (P &lt;0.01). The corresponding KD values at each airway level were similar, i.e. 29 ± 2 and 33 ± 1 pmol/l, respectively. Autoradiography revealed that there was dense labelling of bronchial and bronchiolar epithelium and most strikingly of the alveolar wall.
3. Compared with carcinoma controls, mean Bmax. values in cystic fibrosis were significantly reduced in membrane preparations of both airway levels 1 and 11 (P &lt;0.01). Autoradiography showed the reduction was most apparent in alveolar wall and bronchial epithelium.
4. There was a tendency to reduction of Bmax. in membrane preparations from patients with bronchiectasis at airway level I, but this failed to reach statistical significance. Autoradiography demonstrated that the density of labelling was significantly reduced in bronchial epithelium and bronchial smooth muscle as compared with carcinoma controls (P &lt;0.01).
5. The Bmax. values were not significantly altered in membranes prepared from both airway levels in asthma, albeit there was a tendency towards reduction in Bmax. at level 1. At this level autoradiography demonstrated significantly reduced labelling of bronchial epithelium (P&gt;0.01) and submucosal glands (P&gt;0.05) but not of bronchial smooth muscle.
6. It is most likely that the reduction in β-adrenoceptor number that we have found in cystic fibrosis is secondary to pulmonary infection and airway inflammation. Its relationship to the primary defect remains unclear.
Increased spillover of dopa into arterial blood during dietary salt loading
Authors: Grossman Ehud , Hoffman Aaron , Chang Peter C. , Keiser Harry R. , Goldstein David S. 
Published: August 2015

1. We measured urinary excretion rates of dopamine (3,4-dihydroxyphenethylamine) and dopa (3,4-dihydroxyphenylalanine) and the spillover rate of dopa into arterial blood during dietary salt loading in conscious Dahl salt-sensitive and salt-resistant rats with intact or denervated kidneys.
2. Dopa spillover was calculated from the steady-state clearance of intravenously infused l-[3H]dopa and arterial levels of endogenous dopa.
3. Daily excretion rates of dopa and dopamine increased by about sixfold during salt loading in both rat strains. Bilateral renal denervation delayed these increases and the natriuretic responses.
4. During dietary salt loading, dopa spillover increased to approximately the same extent as simultaneously measured dopamine excretion.
5. The results suggest that increases in urinary excretion of dopamine during dietary salt loading can be accounted for by increases in the release of dopa into the bloodstream and that the renal nerves contribute to the dopa and dopamine excretory responses.
Dissociation between uric acid and urea clearances in the syndrome of inappropriate secretion of antidiuretic hormone related to salt excretion
Authors: Decaux G. , Prospert F. , Cauchie P. , Soupart A. 
Published: August 2015

1. Our purpose was to determine why hypouricaemia is more frequently observed than hypouraemia in the syndrome of inappropriate secretion of antidiuretic hormone. We have retrospectively analysed the scores of 35 patients with a chronic form of hyponatraemia related to the syndrome of inappropriate secretion of antidiuretic hormone and studied prospectively six patients.
2. The patients with high fractional excretion of filtered urea (&gt;55%) presented lower blood urea and lower salt excretion than the patients with normal fractional excretion of filtered urea, despite similar levels of hyponatraemia and of osmotic and uric acid clearances. In six hyponatraemic patients, an increase in salt intake was accompanied by a decrease in fractional excretion of filtered urea. In the syndrome of inappropriate secretion of antidiuretic hormone, the fractional excretion of filtered urea was inversely correlated to the fractional excretion of filtered sodium (r = −0.66; P &lt;0.001), whereas the fractional excretion of filtered uric acid was not dependent on sodium excretion.
3. Hypouraemia with high fractional excretion of filtered urea in patients with the syndrome of inappropriate secretion of antidiuretic hormone is related to low urinary sodium excretion and thus reflects low sodium intake.
Splenic responses to acute insulin-induced hypoglycaemia in humans
Authors: Fisher B. M. , Gillen G. , Hepburn D. A. , Dargie H. J. , Barnett E. , Frier B. M. 
Published: August 2015

1. The effects of acute hypoglycaemia on the spleen were examined in normal humans using radioisotopic techniques, complemented by ultrasonic examination of the spleen. Hypoglycaemia had a modest effect on splenic area, measured by ultrasonography, which declined to 62 ± 6% (mean ± sem) of the basal value after the onset of the acute hypoglycaemic reaction.
2. Hypoglycaemia had a pronounced effect on the splenic radioactivity, which decreased significantly to a mean of 10 ± 7% of basal radioactivity at 15 min after the onset of hypoglycaemia. The splenic image completely disappeared at some time after hypoglycaemia in all subjects.
3. The reduction of splenic radioactivity was abolished during non-selective α-adrenergic blockade with phentolamine, but was unaffected by β-adrenergic blockade with propranolol, or cholinergic blockade with atropine, which suggests that the response of vessels perfusing the spleen is mediated by α-adrenoceptors.
Atrial natriuretic peptide and chronic renal effects of changes in dietary protein and sodium intake in man
Authors: Doorenbos C. J. , Iestra J. A. , Papapoulos S. E. , Odink J. , Van Brummelen P. 
Published: August 2015

1. Plasma levels of atrial natriuretic peptide and several other hormones were measured and related to the renal responses to chronic changes in the dietary intake of protein and sodium, alone and in combination. Eight healthy subjects consumed four diets for 1 week: a basal diet containing 140 mmol of sodium/day and 1 g of protein day−1 kg−1, the same diet with isocaloric addition of 1 g of meat protein day−1 kg−1, the basal diet with addition of 170 mmol of sodium chloride/day and the basal diet with both additions.
2. Creatinine clearance was increased significantly both by protein and, to a smaller extent, by sodium. Plasma atrial natriuretic peptide and the urinary excretion of guanosine 3′:5′-cyclic monophosphate were increased significantly by sodium but were not affected by protein. Protein induced a significant rise in plasma glucagon levels, whereas the rise in somatomedin C (insulin-like growth factor I) just failed to reach statistical significance.
3. These findings demonstrate that atrial natriuretic peptide does not mediate chronic protein-induced hyper-filtration, although it may contribute to the renal effects of sodium. Glucagon and somatomedin C (insulin-like growth factor I) may have contributed to chronic protein-induced hyperfiltration.