bluuebunny/crossref_metadata_2025 huggingface dataset:
Plasma levels of the Lyso-Derivative of Platelet-Activating Factor in Acute Severe Systemic Illness
Authors: Leonelli Fabio M. , Leong Lillian L. , Sturm Marian J. , Strophair Julie A. , Clarke Geoffrey M. , Taylor Roger R.
Published: August 2015

1. Evidence suggests that activation of phospholipase A2 and production of eicosanoids and platelet-activating factor (PAF) are involved in various responses associated with severe tissue damage and shock. It was postulated that the plasma level of the precursor and degradation product of PAF, lyso-platelet-activating factor (lyso-PAF), might be increased in acute severe illness.

2. After plasma extraction, lyso-PAF was acetylated in vitro to PAF, which was measured by bioassay using 5-[14C]hydroxytryptamine-labelled rabbit platelets. Measurements were made in 18 severely ill patients (five with cardiogenic shock; five with severe infection, five after repair of abdominal aortic aneurysm, two with acute pancreatitis; 13 males, five females). Plasma lyso-PAF in these patients was 33 ± 15 (sd) ng/ml (range 5–111 ng/ml), whereas values in normal males (40–65 years) ranged from 102 to 253 ng/ml (n = 15) and in females from 74 to 174 ng/ml (n = 10). Depression of plasma lyso-PAF did not relate closely to the patient group nor to specific therapy, but repeated measurements in each of 10 patients showed an increase in plasma lyso-PAF (P < 0.002), associated with clinical improvement.

3. Evidence was obtained indicating that neither the presence of an inhibitor in the assay system nor reconversion of PAF to lyso-PAF in vitro produced the unexpected depression of plasma lyso-PAF.

4. The mechanisms responsible, which may have therapeutic implications, remain to be elucidated.
Immunoreactive N-terminal Pro-Atrial Natriuretic Peptide in Human Plasma: Plasma Levels and Comparisons with α-Human Atrial Natriuretic Peptide in Normal Subjects, Patients with Essential Hypertension, Cardiac Transplant and Chronic Renal Failure
Authors: Buckley M. G. , Sagnella G. A. , Markandu N. D. , Singer D. R. J. , MacGregor G. A.
Published: August 2015

1. Plasma levels of immunoreactive N-terminal pro-atrial natriuretic peptide (N-terminal ANP) have been measured in 25 normal subjects, 29 patients with essential hypertension, six cardiac transplant recipients, seven patients with dialysis-independent chronic renal failure and 11 patients with haemodialysis-dependent chronic renal failure. Plasma was extracted on Sep-Pak cartridges and N-terminal ANP immunoreactivity was measured using an antibody directed against pro-ANP (1–30).

2. Plasma levels of TV-terminal ANP (means ± sem) were 235.3 ± 19.2 pg/ml in normal subjects and were significantly raised in patients with essential hypertension (363.6 ± 36.3 pg/ml), in cardiac transplant recipients (1240.0 ± 196.2 pg/ml), in patients with chronic renal failure not requiring dialysis (1636.6 ± 488.4 pg/ml) and patients with chronic renal failure on maintenance haemodialysis (10 336.1 ± 2043.7 pg/ml).

3. There were positive and significant correlations between the plasma levels of TV-terminal ANP and α-human ANP (α-hANP) with individual correlation coefficients of 0.68 within the normal subjects, 0.47 in patients with essential hypertension, 0.78 in patients with dialysis-independent chronic renal failure and 0.68 in patients with haemodialysis-dependent chronic renal failure (P < 0.05 in every case).

4. Gel filtration behaviour on Sephadex G-50 of the immunoreactive N-terminal ANP from Sep-Pak extracts of plasma from normal subjects or patients was consistent with a single peak having an elution volume corresponding to that of human pro-ANP (1–67) standard.

5. These studies demonstrate that the N-terminal pro-ANP peptide is co-secreted with α-hANP in both normal subjects and patients with cardiovascular/renal disease. The higher levels of the N-terminal ANP may reflect differences in the rate of elimination from the circulation but the exact structure and functional significance of the circulating N-terminal ANP remains to be established.
Anaesthetic Agents and Their Effect on Tissue Protein Synthesis in the Rat
Authors: Heys S. D. , Norton A. C. , Dundas C. R. , Eremin O. , Ferguson K. , Garlick P. J.
Published: August 2015

1. Rates of protein synthesis were measured, in vivo, in lung, liver, heart and skeletal muscle of young male rats. Groups of rats were exposed for 1 h duration to one of the following anaesthetic regimens: 1.4% halothane, 2.2% halothane, 1.4% halothane in 66% nitrous oxide, intravenous pentobarbitone (20 mg/kg) and intravenous midazolam (18 mg/kg) combined with fentanyl (2 μg/kg). Fractional rates of protein synthesis were determined by injecting [3H]phenylalanine (150 μmol/100 g body weight)

2. Liver protein synthesis was depressed significantly by all regimens, except midazolam/fentanyl, by up to 37.7% of control values. Lung protein synthesis was significantly reduced by all the anaesthetic agents by up to 30% of control rates

3. The effects of the anaesthetic agents on skeletal muscle and heart were small and not statistically significant

4. There was no evidence of ventilatory depression as manifested by changes in arterial blood gas partial pressures of CO2 and O2, except in the group treated with 2.2% halothane.
Age-related changes in the circulating levels of congeners of vitamin K2, menaquinone-7 and menaquinone-8
Authors: Hodges S. J. , Pilkington M. J. , Shearer M. J. , Bitensky Lucille , Chayen J.
Published: August 2015

1. Through the vitamin K1 cycle, phylloquinone is now known to play an active role, not only in relation to prothrombin, but also in the synthesis of bone peptides.

2. The recent development of a sensitive method allowed the demonstration of a deficit of vitamin K1 in the circulation of osteoporotic subjects.

3. Vitamin K2, namely the menaquinones of various chain-lengths, has been shown by others to be more effective than vitamin K1 in the curative rat bioassay.

4. Earlier reports had shown that the concentration of menaquinones in human liver may exceed that of vitamin K1. But previous methods were too insensitive for testing the normal circulating levels of menaquinones in the human.

5. The new sensitive method has now been applied to measuring the circulating levels of vitamin K1 and of two of the menaquinones, namely menaquinone-7 and menaquinone-8.

6. In normal individuals, the circulating levels of vitamin K1 were the same, irrespective of age.

7. In young normal subjects, the combined levels of menaquinone-7 and menaquinone-8 were at least the same as the level of vitamin K1. In elderly normal subjects, there was a marked deficit of menaquinone-8.
Decreased natural killer cell activity in late-onset hypogammaglobulinaemia
Authors: Aparicio-Pagés M. N. , den Hartog G. , Verspaget H. W. , Peña A. S. , van der Meer J. W. M. , van Furth R. , Lamers C. B. H. W.
Published: August 2015

1. Natural killer cell activity and monocyte cytotoxicity was evaluated in three subgroups of patients with primary hypogammaglobulinaemia (ten patients with late-onset, eight with X-linked and five with early-onset disease) and in two patients with secondary late-onset hypogammaglobulinaemia against the K-562 erythro-leukaemia, the CaCo-2 colon carcinoma and the HGT-1 gastric carcinoma cell lines and compared with the results found in healthy control subjects.

2. The natural killer cell activity, both spontaneous and after stimulation with recombinant γ-interferon, was found to be decreased in patients with late-onset hypogammaglobulinaemia. The natural killer cell activity in this subgroup was found to be impaired in 60% of the patients (P < 0.05). Within the other forms of primary hypogammaglobulinaemia a decreased natural killer cell activity was found to be less frequent (33%).

3. The lectin-mediated cytotoxicity by phytohaem-agglutinin resulted in a similar maximal cytotoxicity in patients and control subjects.

4. The cytotoxicity of monocytes, spontaneous and after recombinant γ-interferon stimulation, was found to be normal in all patients with hypogammaglobulinaemia.

5. The impaired natural killer cell activity which was found in patients with late-onset hypogammaglobulinaemia may contribute to the increased susceptibility to infections and to the increased incidence of malignancies in this subgroup of patients with primary hypogammaglobulinaemia.
Increased density of peripheral benzodiazepine-binding sites in ovarian carcinomas as compared with benign ovarian tumours and normal ovaries
Authors: Katz Yeshayahu , Ben-Baruch Gilad , Kloog Yoel , Menczer Joseph , Gavish Moshe
Published: August 2015

1. Benzodiazepines are involved in the control of proliferation and differentiation of normal and malignant cells in vitro. This regulatory ability is probably mediated via peripheral benzodiazepine-binding sites.

2. In the present study we compared the binding characteristics of peripheral benzodiazepine-binding sites in human epithelial ovarian carcinoma with those in benign ovarian tumours and normal ovaries.

3. The affinity and density of peripheral benzodiazepine-binding sites in homogenate preparations of ovarian carcinoma as compared with benign ovarian tumours and with normal tissues (used as controls) were determined using a ligand specific for peripheral benzodiazepine-binding sites, [3H]PK 11195, an isoquinoline carboxamide derivative.

4. We observed a robust (three-to five-fold) increase in the neoplasm compared with benign ovarian tumours and normal tissues, without a concomitant change in affinity values.

5. This finding may reflect a change in the metabolic rates of ovarian cancer which is expressed as the alteration in the density of peripheral benzodiazepine-binding sites.
Effects of circulating endogenous catecholamines on plasma glucose, potassium and magnesium
Authors: Corr L. A. , Grounds R. M. , Beacham J. L. , Whitwam J. G. , Brown M. J.
Published: August 2015

1. To examine the metabolic effects of increases in circulating endogenous plasma catecholamines, we measured plasma glucose, potassium and magnesium in 14 patients undergoing elective coronary artery bypass grafting. The patients were randomized into two groups and received either sodium nitroprusside (a direct-acting vasodilator) or trimetaphan camsylate (a ganglion-blocking agent) for routine control of blood pressure during the operation.

2. There were significant differences between the two groups in the levels of all three metabolic variables studied. Plasma glucose levels rose in both groups, but were significantly higher in the sodium nitroprusside group [peak levels 9.14 (sem 0.72)mmol/l compared with 6.71 (0.88) mmol/l, P< 0.001, analysis of variance]. The cardioplegia solution caused a large increase in plasma magnesium in both groups but in the sodium nitroprusside group the level rose higher [to 1.59 (0.12)mmol/l compared with 1.34 (0.06)mmol/l] and fell faster (P < 0.05, analysis of variance). In the group receiving sodium nitroprusside, plasma potassium fell, by a mean of 0.34 mmol/l, as plasma catecholamine levels rose; no such fall was seen in the group receiving trimetaphan camsylate (P < 0.05, analysis of variance).

3. It is concluded that the sympathoadrenal system is important in causing metabolic changes during cardiopulmonary bypass and may be relevant in other conditions such as acute myocardial infarction.
Regulation of nicotinamide–adenine dinucleotide synthesis in erythrocytes of patients with hypoxanthine–guanine phosphoribosyltransferase deficiency and a patient with phosphoribosylpyrophosphate synthetase superactivity
Authors: Micheli Vanna , Simmonds H. Anne , Ricci Carlo
Published: August 2015

1. The synthesis of nicotinamide–adenine dinucleotide from nicotinamide and nicotinic acid was compared over different time scales at both physiological (0.7 μmol/l) and high (0.2–3 mmol/l) substrate concentrations in erythrocytes from three patients with hypoxanthine–guanine phosphoribosyltransferase (hypoxanthine phosphoribosyltransferase, EC 2.4.2.8) deficiency (including one Lesch–Nyhan patient) and from one patient with phosphoribosylpyrophosphate synthetase superactivity. The above disorders are associated with grossly altered erythrocyte nicotinamide-adenine dinucleotide levels.

2. At the physiological substrate concentration and incubation times up to 2 h, nicotinamide proved the most efficient nicotinamide–adenine dinucleotide precursor for erythrocytes from both patients and control subjects. The conversion of nicotinamide to its mononucleotide, but not further metabolism, was impaired in phosphoribosylpyrophosphate synthetase-mutant cells. The Lesch–Nyhan and phosphoribosylpyrophosphate synthetase-mutant cells were unusual in that both showed no further stimulation of nucleotide synthesis at 18 mmol/l Pi compared with 1 mmol/l.

3. At the high substrate concentrations, using 18 mmol/l Pi, nicotinamide was a poor precursor in all instances. Using nicotinic acid, nucleotide formation was 30-fold that from nicotinamide, reaching its maximum at 0.2 mmol/l. Conversion of nicotinic acid to nicotinamide–adenine dinucleotide in the phosphoribosylpyrophosphate synthetase-mutant cells was again grossly impaired.

4. There was no evidence for increased nicotinamide–adenine dinucleotide breakdown in the phosphoribosylpyrophosphate synthetase-mutant cells under any of the above conditions.

5. These results suggest that the differing nicotinamide–adenine dinucleotide levels in the two disorders cannot be related directly to the altered phosphoribosylpyrophosphate levels. The problem appears to be one of decreased synthesis in the phosphoribosylpyrophosphate synthetase-mutant cells, whereas the synthetic capacity in intact hypoxanthine–guanine phosphoribosyltransferase-deficient cells is neither enhanced nor inhibited by the raised nicotinamide–adenine dinucleotide levels.
Electrocardiographic changes induced by inhaled salbutamol after treatment with bendrofluazide: Effects of replacement therapy with potassium, magnesium and triamterene
Authors: Lipworth B. J. , McDevitt D. G. , Struthers A. D.
Published: August 2015

1. Twelve normal subjects were given 5 days' treatment with (a) placebo; (b) 5 mg of bendrofluazide; (c) 5 mg of bendrofluazide plus 24 mmol of potassium; (d) 5 mg of bendrofluazide plus 24 mmol of magnesium; (e) 5 mg of bendrofluazide plus 24 mmol of potassium plus 24 mmol of magnesium; (f) 5 mg of bendrofluazide plus 50 mg of triamterene.

2. After each treatment period, subjects were given two doses of inhaled salbutamol (each of 1 mg), and measurements were made 25 min after each dose.

3. Treatment with bendrofluazide plus salbutamol produced a lower absolute level of plasma potassium than salbutamol alone, although the addition of potassium, magnesium or triamterene did not attenuate this effect. Plasma magnesium was unchanged by salbutamol.

4. Salbutamol was associated with significant electrocardiographic effects, including T-wave flattening, Q-Tc interval prolongation and, in some subjects, U-waves and S-T segment depression.

5. Prior treatment with bendrofluazide potentiated the electrocardiographic effects of salbutamol. Supplementation with potassium and magnesium had no effect on electrocardiographic changes, and the addition of triamterene to bendrofluazide only attenuated electrocardiographic responses in some subjects.
Total-body potassium in insulin-dependent diabetes mellitus
Authors: Goodship T. H. J. , Butler P. C. , Rodham D. , Clayton B. , Home P. D. , Alberti K. G. M. M.
Published: August 2015

1. Total-body potassium and fat-free mass have been measured in 31 insulin-dependent diabetic patients and 31 age- and sex-matched normal volunteers.

2. Body mass index was significantly higher in the insulin-dependent diabetic patients (24.7 ± .5 vs 23.3 ± 0.4 kg/m2; P = 0.05).

3. Total-body potassium, uncorrected and corrected for weight and for fat-free mass, was not significantly different in the two groups (3281 ± 141 mmol, 47.3 ± 1.3 mmol/kg body weight, 60.9 ± 1.0 mmol/kg fat-free mass, and 3315 ± 143 mmol, 48.6 ± 1.0 mmol/kg body weight, 60.4 ± 0.8 mmol/kg fat-free mass, respectively, in diabetic patients and non-diabetic subjects). There was no relationship between blood glucose control, as assessed by glycated haemoglobin concentrations, and total-body potassium.

4. These results suggest, by contrast with previous reports, that in insulin-dependent diabetic patients, showing varying degrees of glycaemic control (glycated haemoglobin range 6.1–15.3%, mean 9.0%) that: (a) there is no significant abnormality of body potassium homoeostasis, and (b) there is no relation between total-body potassium and glycaemic control.
Abnormal arterial flow pattern in untreated essential hypertension: Possible link with the development of atherosclerosis
Authors: Jones Christopher J. H. , Singer Donald R. J. , Watkins Nicholas V. , MacGregor Graham A. , Caro Colin G.
Published: August 2015

1. We compared the velocity waveforms in the superficial femoral artery measured by multichannel Doppler ultrasound in 45 subjects: 21 patients with untreated essential hypertension and 24 normal subjects of similar age and sex.

2. The pattern of arterial flow was abnormal in hypertensive patients, with the acceleration time, the duration of reverse flow and the time to maximum flow reversal being abbreviated. The internal arterial diameter, calculated from the velocity profile, was reduced despite raised pressure, suggesting altered arterial wall mechanics in essential hypertension.

3. These abnormalities will influence the wall shear stress, a major determinant of arterial function. The abnormal arterial wall mechanics and abnormal blood flow pattern may contribute to the increased risk of arterial disease in patients with untreated hypertension.
Overall renal and tubular function during infusion of amino acids in normal man
Authors: Olsen N. V. , Hansen J. M. , Ladefoged S. D. , Fogh-Andersen N. , Nielsen S. Levin , Leyssac P. P.
Published: August 2015

1. Amino acids have been used to test renal reserve filtration capacity. Previous studies suggest that amino acids increase glomerular filtration rate (GFR) by reducing distal tubular flow and tubuloglomerular feedback activity.

2. Glomerular function and the renal tubular handling of sodium during infusion of amino acids was studied in 12 normal volunteers.

3. Clearance of sodium (CNa) was unchanged. Effective renal plasma flow increased slightly, but significantly, by 9% (P <0.05). GFR was increased by 13% (P <0.001). Clearance of lithium (CLi) (used as an index of proximal tubular outflow) increased by 38% (P <0.001). Calculated absolute proximal reabsorption (GFR-CLi) remained unchanged. Fractional proximal reabsorption [1-(CLi/GFR)] was decreased by 10% (P <0.001). Calculated absolute distal sodium reabsorption [(CLi–CNa) × PNa, where PNa is plasma sodium concentration] increased by 40% (P <0.001). Plasma renin concentration did not change significantly.

4. The results suggest that amino acids increase GFR by a primary effect on renal haemodynamics or, less likely, by reducing the signal to the tubuloglomerular feedback mechanism. The increase in proximal tubular outflow was compensated for in the distal tubules, so that the sodium excretion rate remained unchanged.
Attenuation of the low-density-lipoprotein-activated phosphoinositide signalling system by calcium blockers in human lymphocytes
Authors: Locher Rudolf , Sachinidis Agapios , Steiner Albert , Vetter Wilhelm
Published: August 2015

1. The capacity of low-density lipoprotein-cholesterol (40 μg/ml) to stimulate both the phosphoinositide cycle and the dislocation of the phospholipid- and calcium-dependent protein kinase C activity from the cytosolic to the membranous compartment in human circulating lymphocytes has been studied.

2. Pretreatment of lymphocytes with pertussis toxin inhibited significantly the low-density-lipoprotein-induced formation of inositol trisphosphate.

3. The calcium-channel blockers verapamil, nifedipine and diltiazem, each in a concentration range from 1 μmol/l to 1 nmol/l, attenuated the low-density lipoprotein-induced formation of inositol trisphosphate in a dose-dependent manner. Similar results were observed when so-called non-specific calcium antagonists, such as flunarizine and molsidomine, were used.

4. The results suggest that low-density lipoprotein activates the phosphoinositide cycle in circulating lymphocytes through mechanisms sensitive to calcium blockers and pertussis toxin.
Differential binding of serum glycoproteins to lectins during hepatic regeneration in hepatocellular carcinoma and fulminant hepatic failure
Authors: Du M.-Q. , Hutchinson W. L. , Johnson P. J. , Williams Roger
Published: August 2015

1. The concentrations of four serum glycoproteins, thyroxine-binding globulin, α2-macroglobulin, α1-antitrypsin and transferrin, as well as their reactivities with concanavalin A and lentil-lectin, were measured in patients with hepatocellular carcinoma or fulminant hepatic failure and in normal subjects.

2. Serum concentrations of thyroxine-binding globulin and α1-antitrypsin were significantly greater in patients with hepatocellular carcinoma than in normal subjects, and the percentage lentil-lectin reactivity of these two proteins was markedly increased.

3. With the exception of transferrin, which did not bind to lentil-lectin, an enhancement of lentil-lectin reactivity was observed for the glycoproteins in serum from patients with fulminant hepatic failure. No difference in concanavalin A binding was found between the groups for any of the glycoproteins.

4. Altered fucosylation, as indicated by increased lentil-lectin binding, occurs in several glycoproteins arising in malignant and non-malignant conditions associated with abnormal hepatic regeneration.
Effect of Urate on Calcium Oxalate Crystallization in Human Urine: Evidence for a Promotory Role of Hyperuricosuria in Urolithiasis
Authors: Grover Phulwinder K. , Ryall Rosemary L. , Marshall Villis R.
Published: August 2015

1. The effect of hyperuricosuria, simulated by increasing the concentration of dissolved urate, on the crystallization of calcium oxalate in human urine was examined.

2. Twenty urine samples were studied. Ten of these, designated type A, spontaneously precipitated calcium oxalate dihydrate crystals upon the addition of a solution of sodium urate solution which raised the median urate concentration from 3.1 to 7.0 mmol/l.

3. Adding dissolved urate to the remaining type B samples raised the median urate concentration from 2.2 to 6.2 mmol/l, but did not cause the precipitation of calcium oxalate. This was induced in these samples by the addition of a standard load of oxalate above an empirically determined metastable limit.

4. In the type B urine samples, the addition of urate decreased the median metastable limit from 125 to 66 μmol of oxalate, trebled the median volume of crystalline calcium oxalate deposited from 35 000 to 105 000 μm3/μl and significantly increased the overall size of the particles precipitated. Calcium oxalate monohydrate was exclusively precipitated, and the individual crystals deposited in the presence of urate were markedly smaller, more numerous, and more highly aggregated than those produced in its absence.

5. These results constitute the most convincing evidence yet obtained that hyperuricosuria may be a powerful promoter of calcium oxalate stone formation.
Role of Atrial Natriuretic Factor in Changes in the Responsiveness of Aldosterone to Angiotensin II Secondary to Sodium Loading and Depletion in Man
Authors: Tuchelt H. , Eschenhagen G. , Bähr V. , Schwietzer G. , Thiede H. M. , Oelkers W.
Published: August 2015

1. Sodium loading blunts the response of aldosterone to infusion of angiotensin II, whereas sodium depletion leads to an enhanced response. The hypothesis was tested that these changes in responsiveness of the zona glomerulosa are mediated in part by changes in plasma atrial natriuretic factor levels.

2. To this end, plasma renin activity and plasma aldosterone were measured in the upright and recumbent position and during incremental infusions of angiotensin II (1, 3 and 6 ng of angiotensin II amide min−1 kg−1 for 1 h each dose) after 6 days of sodium loading (study 1), after 5 days of sodium depletion (study 2) and after sodium depletion plus infusion of atrial natriuretic factor (0.13 μg/min for 8 h) on the test day (study 3). Six normal young males were investigated.

3. Plasma atrial natriuretic factor levels were around 5 pmol/l in study 2, 15 pmol/l in study 1 and 15 pmol/l in study 3 during infusion of atrial natriuretic factor. Two hours after the onset of atrial natriuretic factor infusion, plasma renin activity and plasma aldosterone (recumbent) were markedly and significantly lower in study 3 than in study 2, but still significantly higher than in study 1. The increase in plasma aldosterone after infusion of angiotensin II was slightly, but not significantly, blunted by infusion of atrial natriuretic factor in study 3 compared with study 2. The overall increase in plasma aldosterone was still significantly greater in study 3 than in study 1.

4. The fall in renal plasma flow, determined as p-aminohippurate clearance, during infusion of angiotensin II was greater in study 1 than in studies 2 and 3. Small differences between study 3 and study 2 were not significant.

5. It is concluded that infusions of atrial natriuretic factor in the low-sodium state that mimic plasma atrial natriuretic factor levels after sodium loading lead to a marked fall in recumbent plasma aldosterone, which is to a large extent secondary to a fall in plasma renin activity. A small direct effect of these physiologically elevated atrial natriuretic factor levels on the zona glomerulosa itself (the increase in plasma aldosterone during angiotensin II infusion) was only of borderline significance. Thus, atrial natriuretic factor at physiological plasma concentrations is a regulator of renin and aldosterone secretion, whereas a modulating effect on the renal vasoconstrictor action of angiotensin II could not be demonstrated.
Sodium and Water Excretion in Nephrotic Patients: Effects of Changes in Renal Haemodynamics
Authors: Allon Michael , Pasque Charles B. , Rodriguez Mariano
Published: August 2015

1. Eight nephrotic patients were studied in order to evaluate the effects of acute changes in renal plasma flow and glomerular filtration rate on renal solute and water handling, in the absence of plasma volume expansion.

2. The subjects were studied first after the administration of captopril, a manoeuvre that increased renal plasma flow without a significant change in glomerular filtration rate, and a second time after receiving combined therapy with captopril and ibuprofen, a manoeuvre that decreased glomerular filtration rate without a significant change in renal plasma flow.

3. After captopril therapy, despite the increase in renal plasma flow, there was no significant change in proximal sodium reabsorption (as estimated from fractional lithium reabsorption), urine volume or urine osmolality.

4. The decrease in glomerular filtration rate observed after the administration of captopril plus ibuprofen was associated with decreases in fractional excretion of sodium and urine volume, and an increase in urine osmolality. The changes in these parameters of tubular function were proportionate to the changes in glomerular filtration rate. Fractional proximal sodium reabsorption increased substantially.

5. These observations suggest that, in the absence of plasma volume expansion, an increase in renal plasma flow does not increase sodium or water excretion by the nephrotic kidney. Moreover, during acute decreases in glomerular filtration rate, glomerulotubular balance appears to be disrupted, resulting in disproportionately high rates of proximal tubule sodium reabsorption.
Effects of Oxygen Withdrawal on Catecholamine Release in Patients on Home Oxygen Therapy
Authors: Balter M. S. , Chapman K. R. , Maleki-Yazdi M. R. , Leenen F. H. H. , Rebuck A. S.
Published: August 2015

1. Long-term oxygen therapy in appropriate patients prolongs survival and corrects neuropsychological function. Some tests of mental function paradoxically improve during short periods of oxygen withdrawal in patients on long-term oxygen therapy, although the mechanism of this response is unknown.

2. To evaluate the effects of transient hypoxaemia on plasma adrenaline and noradrenaline levels, we studied eight oxygen-dependent patients who underwent either a 4 h period of oxygen withdrawal or their routine therapy, in a randomized, blinded fashion, on 2 separate days.

3. Plasma noradrenaline did not differ at baseline between study days. During normoxic conditions, plasma noradrenaline levels did not increase significantly with time. By contrast, under hypoxic conditions, plasma levels of noradrenaline rose significantly from 0 to 4 h (P < 0.05). The magnitude of the noradrenaline response was correlated with baseline noradrenaline such that subjects with the highest resting levels had the largest increase during hypoxia (r = 0.95, P < 0.001).

4. Plasma adrenaline did not differ at baseline between study days and there were no significant effects of hypoxia on plasma adrenaline levels.

5. We conclude that the sympathetic nervous system, but not the adrenal medulla, is stimulated in chronically oxygen-dependent subjects made acutely hypoxaemic. The magnitude of this stimulation appears to be related to the state of sympathetic nervous system activity at baseline. Improvement in some tests of mental function during transient periods of oxygen withdrawal may be due to non-specific arousal caused by a catecholamine surge.
Effects of Isosorbide Dinitrate on the Pattern of Arterial Blood Flow in Healthy Human Subjects
Authors: Caro C. G. , Fish P. J. , Goss D. E. , Halls J. , Lever M. J. , Parker K. H. , Clear A. Stacey
Published: August 2015

1. Blood velocity measurements have been made in the superficial femoral artery, 10 cm downstream of the common femoral artery bifurcation, in healthy human subjects, using a multi-channel Doppler ultrasound device.

2. In a randomized double-blind protocol, the effects of isosorbide dinitrate were examined during a 2 h period.

3. The changes induced by isosorbide dinitrate include: (i) an increase in the width of the artery and a reduction in brachial arterial blood pressure, implying relaxation of arterial smooth muscle; (ii) an increase in reverse flow and a decrease in time-averaged mean velocity associated with a relatively small decrease of the velocity excursion during the cardiac cycle, implying an increase in flow pulsatility; and (iii) an alteration of the flow pattern both in the core and near the vessel walls.
Cellular and Muscle Zinc in Surgical Patients with and without Gastrointestinal Cancer
Authors: Goode Helen F. , Kelleher Jerry , Walker Barry E. , Hall Richard I. , Guillou Pierre J.
Published: August 2015

1. The zinc status of surgical patients with and without gastrointestinal cancer was studied.

2. Plasma zinc was lowest in patients with cancer concurrent with depressed plasma albumin concentrations.

3. Polymorphonuclear cell zinc was decreased in both patient groups and correlated strongly with abdominal muscle zinc (r = 0.89, P < 0.001).

4. Mononuclear cell and total leucocyte zinc were similar to control values in both groups of patients. Total leucocyte, but not mononuclear cell, zinc correlated weakly with muscle zinc (r = 0.48, P < 0.05).

5. The results suggest that polymorphonuclear cell zinc may be better than leucocyte zinc in assessing zinc status and that some surgical patients may be zinc-depleted. The presence of gastrointestinal cancer did not influence the zinc status.
Effect of Nifedipine on Renal Haemodynamics in an Animal Model of Cyclosporin a Nephrotoxicity
Authors: McNally P. G. , Baker F. , Mistry N. , Walls J. , Feehally J.
Published: August 2015

1. This study investigates the effect of nifedipine on cyclosporin A nephrotoxicity in the spontaneously hypertensive rat.

2. Cyclosporin A, administered daily by subcutaneous injection at 25 mg/kg body weight for 14 days, induced a significant reduction in glomerular filtration rate (35.3%) and effective renal plasma flow (45.0%), and an increase in renal vascular resistance (219%). Using this regimen, tubular, glomerular or vascular morphological damage was not evident on light microscopy.

3. The administration of nifedipine simultaneously with cyclosporin A from day 1 prevented the characteristic decline in renal function and increase in renal vascular resistance. However, the administration of nifedipine to spontaneously hypertensive rats previously exposed to cyclosporin A for 7 days failed to improve renal haemodynamics.

4. This study suggests that the beneficial effect conferred by nifedipine on cyclosporin A nephrotoxicity is present only when treatment is initiated simultaneously with cyclosporin A.
Effect of NG-Monomethyl-l-Arginine on Endothelium-Dependent Relaxation of Human Subcutaneous Resistance Arteries
Authors: Woolfson Robin G. , Poston Lucilla
Published: August 2015

1. Using a myograph to measure isometric tension, we have looked at the action of NG-monomethyl-l-arginine on the endothelium-dependent relaxation of human subcutaneous resistance arteries.

2. NG-Monomethyl-l-arginine, the novel inhibitor of endothelium-derived relaxing factor synthesis, caused concentration-dependent but only partial inhibition of maximal relaxation induced by acetylcholine in human subcutaneous resistance arteries.

3. The inhibitory action of NG-monomethyl-l-arginine on acetylcholine-induced maximal relaxation was partially reversed by incubation of the arteries in equimolar concentrations of l-arginine and NG-monomethyl-l-arginine. Subsequent incubation in l-arginine led to further reversal, but this was no greater than with incubation in physiological saline.

4. A component of acetylcholine-induced relaxation was sensitive to indomethacin, suggesting that this response is mediated by prostanoids as well as by endothelium-derived relaxing factor.

5. NG-Monomethyl-l-arginine did not increase the tension of resting human subcutaneous resistance arteries. NG-Monomethyl-l-arginine did enhance the contractile response to noradrenaline, possibly due to inhibition of release of endothelium-derived relaxing factor resulting from stimulation of α2-adrenoreceptors on the endothelial cells.
Effect of a Test Meal, without and with Protein, on Muscle and Plasma Free Amino Acids
Authors: Bergström J. , Fürst P. , Vinnars E.
Published: August 2015

1. The effect of a protein-free meal and a protein-rich meal on the concentration of free amino acids in plasma and muscle tissue was studied in eight healthy subjects. The energy content of the protein-free meal was 3800 kJ. The protein-rich meal was identical in composition except that 50 g of bovine serum albumin was added. Plasma and samples from the quadriceps femoris muscle (percutaneous muscle biopsy) for amino acid determination were collection before and at 1, 3, 5 and 7 h after the meal.

2. After the protein-free meal the concentrations of most essential amino acids and of some non-essential amino acids in plasma decreased continuously below basal levels at 5–7 h. The muscle concentration of essential amino acids fell too, reaching its nadir 3–5 h after the meal. The decrease in plasma amino acid concentration was smaller than the decrease in muscle concentration for all essential amino acids except phenylalanine.

3. The concentrations of most amino acids in plasma increased transiently 1 and 3 h after the protein-rich meal; histidine and several non-essential amino acids fell below the basal levels at 5–7 h after the meal. In muscle, threonine, valine, leucine, lysine and alanine were increased at 1 and 3 h after the protein-rich meal; isoleucine, serine and glycine fell below the basal level after 5 and 7 h. For the essential amino acids except threonine and lysine, the increase in plasma concentration was greater than the increase in muscle concentration.

4. Correlations were observed between the relative content of the essential amino acids in the bovine serum albumin and the increase in concentration of these amino acids in plasma and muscle. Methionine and isoleucine, which had the lowest content in bovine serum albumin, fell below basal levels in plasma and (for isoleucine) in muscle 5–7 h after the meal, suggesting that these two amino acids might have been limiting for protein synthesis.

5. Amino acid analysis in plasma and muscle samples taken postprandially should be evaluated with caution considering the strong influence of meal composition on plasma and muscle free amino acid profiles.
Effect of Cardiac Tamponade on Atrial Natriuretic Peptide Concentrations: Influence of Stretch and Pressure
Authors: Au J. , Brown J. E. , Lee M. R. , Boon N. A.
Published: August 2015

1. In order to study the role of atrial pressure and atrial stretch on the release of atrial natriuretic peptide we have measured plasma atrial natriuretic peptide concentration, urine output and haemodynamic variables in eight patients during and 30 min after the relief of cardiac tamponade. This condition is characterized by high atrial pressure with little or no atrial stretch.

2. Relief of tamponade was associated with a rise in urine output (53 ± 27.9 to 101 ± 24.5 ml/h, mean ± sem; P = 0.09), systolic blood pressure (95 ± 9.6 to 126 ± 7.0 mmHg, P < 0.0001), and plasma atrial natriuretic peptide concentration (369.5 ± 70.9 to 490.3 ± 94.7 pg/ml, P < 0.05) despite a large fall in right atrial pressure (18.6 ± 1.6 to 9.5 ± 1.3 mmHg, P < 0.001).

3. These results suggest, therefore, that an increase in atrial stretch, rather than in atrial pressure, stimulates the release of atrial natriuretic peptide.
Differential Effects of Amino Acids on the Isolated Perfused Rat Kidney
Authors: El Sayed A. A. , Haylor J. , El Nahas A. M.
Published: August 2015

1. The direct effects of individual amino acids, including glycine (a neutral amino acid), l-glutamic acid (an acidic amino acid), l-leucine (a neutral, branched-chain amino acid) and l-arginine (a basic amino acid), on renal function were compared with a mixed amino acid solution by using the isolated rat kidney perfused with a physiological saline solution containing 6.7% (w/v) albumin and a basal level of 2 mmol/l mixed amino acids.

2. In a control series, the renal perfusate flow was stable but the glomerular filtration rate, as measured by [14C]inulin clearance, declined with time. A stable glomerular filtration rate could be obtained by increasing the basal perfusate amino acid concentration to 14 mmol/l.

3. The addition of 6 mmol/l mixed amino acids produced a sustained increase in renal perfusate flow and an increase in [14C]inulin clearance, reversing its time-dependent fall. Sodium reabsorption was enhanced, but, unlike the control series, no increase in fractional albumin excretion was obtained.

4. Renal perfusate flow was increased by glycine (6 mmol/l), l-arginine hydrochloride (6 mmoll) and sodium glutamate (6 mmol/l) but remained unaffected by l-leucine. The vasodilatation induced by l-arginine hydrochloride and sodium glutamate was not sustained.

5. The time-dependent fall in [14C]inulin clearance was prevented by glycine, l-arginine and glutamic acid, but not by l-leucine. l-Arginine hydrochloride, like the mixed amino acid solution, produced a significant increase in [14C]inulin clearance.

6. The fractional reabsorption of sodium was increased by glycine and l-leucine, was unaffected by sodium glutamate and was decreased by l-arginine hydrochloride. The time-dependent fall in the fractional excretion of albumin seen in the control series was, however, reversed by all individual amino acids.

7. The results indicate that amino acids can produce renal vasodilatation and hyperfiltration by a direct effect on the kidney, independent of the release of systemic hormones. Individual amino acids, however, differ in their contribution to the response elicited by a mixed amino acid solution. The use of individual amino acids to mimic the renal response to dietary protein in vivo may therefore be inappropriate.
Epidermal Growth Factor Stimulates Synthesis and Secretion of Mucus Glycoproteins in Human Gastric Mucosa
Authors: Kelly S. M. , Hunter J. O.
Published: August 2015

1. The effects of epidermal growth factor on the synthesis and secretion by human gastric mucosa of radiolabelled mucus glycoprotein have been studied in organ culture.

2. Addition of epidermal growth factor at a concentration of 5 or 10 ng/ml increased the synthesis of glycoprotein from 84 ± 16.2 d.p.m./μg of protein to 132 ± 19.5 and 156 ±20.2 d.p.m./μg of protein, respectively. The same doses increased secretion from 73.75 ± 17 d.p.m./μg of protein to 114.0 ± 26.4 and 141.5 ±31.4 d.p.m./μg of protein (P < 0.001).

3. As glycoproteins are the main constituent of the mucus defence barrier, epidermal growth factor-stimulated mucus production may contribute to gastric cytoprotection.
Effects of Acute and Chronic Ethanol Administration and its Withdrawal on the Level and Binding of Somatostatin in Rat Brain
Authors: Barrios V. , Rodríguez-Sánchez M. N. , Arilla E.
Published: August 2015

1. Acute ethanol administration resulted in an increase in the total number of specific somatostatin receptors in rat frontoparietal cortex and hippocampus, and a decrease in the level of somatostatin-like immuno-reactivity in the hippocampus but not in the frontoparietal cortex.

2. Chronic administration of ethanol caused a decrease in the number of somatostatin receptors in the frontoparietal cortex but not in the hippocampus, although the level of somatostatin-like immunoreactivity was unchanged in both brain areas.

3. A week after suppressing ethanol the value for specific binding of tracer to somatostatin receptors in the frontoparietal cortex was not significantly different from that of the control rats, although the actual number of receptors was slightly lower.

4. These results suggest a possible role for somatostatin in the nervous system during alcoholism and the post-withdrawal reaction.
Increased Plasma Histamine Levels in Uraemic Pruritus
Authors: Stockenhuber Felix , Kurz Robert W. , Sertl Kaspar , Grimm Georg , Balcke Peter
Published: August 2015

1. We determined plasma levels of histamine in uraemic patients and examined their correlation with the presence of pruritus.

2. In 27 patients with chronic renal failure, plasma histamine levels were analysed by radioimmunoassay and were compared with those of 40 healthy adult subjects. The control population showed plasma histamine concentrations of 185 ∓ 33 pg/ml, which were significantly lower than those of the patients with renal insufficiency. The highest levels (552 ± 116 pg of histamine/ml) were found in 16 patients with chronic renal failure (mean serum creatinine 5.1 ∓ 1.0 mg/dl) and severe itching.

3. Twelve patients with pronounced pruritus who were on maintenance haemodialysis (serum creatinine 9.2 ±1.2 mg/dl) had a mean plasma histamine concentration of 515 ± 81 pg/ml. Fifteen patients on regular haemodialysis (serum creatinine 9.0 ± 1.5 mg/dl) and who experienced itching had plasma histamine levels (322 ±40 pg/ml) which were significantly lower (P < 0.01) than those of the patients with pruritus but which were elevated compared with those of the control population (P < 0.01).

4. No correlation could be found between increased plasma histamine levels and the type of dialysis membrane used or the method of sterilization of the membrane.

5. Haemodialysis alone did not reduce plasma histamine concentrations, although high concentrations could be detected in the ultrafiltrate. In six patients a rapid decrease in plasma histamine concentration from 565 ∓ 134 pg/ml to within the normal range could be detected after 60 min of combined haemodialysis and haemoperfusion.

6. Our results show that increased plasma levels of histamine are found in patients with renal insufficiency and pruritus, and we conclude that this mediator might be involved in the genesis of uraemic pruritus.
Kinetics of the Human Lymphocyte Na+-H+ Exchanger
Authors: Strazzullo Pasquale , Canessa Mitzy
Published: August 2015

1. A human lymphocyte preparation, obtained by Percoll gradient centrifugation and free of contaminating monocytes and granulocytes, was used to study the kinetics of the Na+-H+ exchanger through activation by nigericin-induced acidic loading. The fluorescent probe biscarboxyethylcarboxyfluorescein (acetoxymethyl ester) was used to determine cell pH and buffering capacity and to measure Na+-H+ exchange activity as external Na+-dependent H+ efflux.

2. At a cell pH of 6.2, H+ efflux was stimulated by external Na+ with a Km of 30 mmol/l (sem 6, n = 3) and a calculated Vmax of 0.73 mmol s−1 l−1 of cell water (sem 0.06, n = 6). External Na+-dependent H+ efflux was more than 98% inhibited and half-maximally inhibited by 200 μmol/l and 17 μmol/l amiloride, respectively. The external pH also inhibited Na+-H+ exchange, with a Ki of 93 nmol/l.

3. Na+-H+ exchange was sigmoidally activated by an internal pH lower than 7.0 with a Hill coefficient of 2.14 (sem 0.15, n = 6) and a pK of 6.57 (sem 0.03, n = 6). Cell buffering capacity was also measured as a function of cell pH and found to gradually increase from 14 to 26 mmol l−1 of cell water pH−1 when cell pH fell below 6.6. The maximal transport rate (cell pH 6.0–6.2) was 0.50 mmol (s 1 of cell water)−1 (sem 0.08, n = 12) and ranged between 0.25 and 1.10.

4. These results indicate that the human blood lymphocyte has a powerful Na+-H+ exchanger which is reproducibly activated by internal acidification with marked inter-individual variability in maximal rate and degree of co-operativity. This technique will be useful for future clinical, functional and genetic studies of the regulation of this antiporter.
Protein Turnover in Uraemia in the Rat
Authors: Ireland S. B. , Stewart P. M.
Published: August 2015

1. The effect of uraemia on the rates of protein synthesis and protein degradation in liver, heart and vastus lateralis muscle were examined in the rat. Uraemia was induced by a five-sixths nephrectomy and the rates of protein turnover were compared with pair-fed sham-operated littermate controls.

2. The procedure produced plasma concentrations (means ±sem) of urea of 7.3 ±0.4 mmol/l in control and 39 ± 2 mmol/l in uraemic rats, and of creatinine of 41 ± 1 μmol/l in control and 133 ± 7 μmol/l in uraemic rats.

3. Uraemia reduced the rates of protein synthesis in liver, heart and muscle by 35 ±5, 4.0 ±1.2 and 4.0 ± 0.6%/day, respectively, compared with control rats (P < 0.01). Since the reductions in tissue growth rate were too small to be accounted for by the reduction seen in protein synthesis alone, this implied that protein degradation was also reduced. Uraemia also caused an 18% reduction in the rate of growth as measured by the increase in tail length (P < 0.01).

4. Uraemia reduced both protein synthesis and protein degradation. Protein synthesis exceeded protein degradation in all tissues. This would cause a reduced rate of protein accumulation in the uraemic compared with the control rats, and hence a reduced rate of growth.