bluuebunny/crossref_metadata_2025_split huggingface dataset:
Tubular reabsorption of pepsinogen isozymogens in man studied by the inhibition of tubular protein reabsorption with dibasic amino acids
Authors: ten Dam M. A. G. J. , Zwiers A. , Crusius J. B. A. , Pals G. , van Kamp G. J. , Meuwissen S. G. M. , Donker A. J. M. , ten Kate R. W. 
Published: August 2015

1. The fractional clearances of pepsinogen A (PGA), pepsinogen C (PGC) and the main PGA isozymogens, i.e. PGA-3, PGA-4 and PGA-5, were measured in 13 healthy male volunteers before and during blockade of tubular protein reabsorption by intravenous infusion of either l-arginine hydrochloride (n = 8; 0.5 g h−1 kg−1 body weight) or an equimolar amount of l-lysine hydrochloride (n = 5; 0.44 g h−1 kg−1 body weight). Glomerular filtration rate was measured by a radioisotope method.
2. The fractional baseline clearance of PGC (1 ± 1%) was lower than that of PGA (20 ± 10%). In addition, the fractional clearance of the PGA isozymogens appeared to be different: the fractional clearance of PGA-5 (7 ± 3%) was lower than that of PGA-4 (18 ± 9%), and the fractional clearance of PGA-4 was lower than that of PGA-3 (30 ± 10%). These differences in fractional clearance between PGA isozymogens decreased during infusion of both arginine and lysine.
3. Pepsinogens are freely filtered proteins. It can therefore be concluded that the differences in fractional clearance between PGA isozymogens imply differences in tubular reabsorption. This is remarkable as PGA isozymogens are proteins with an almost identical amino acid sequence and electric charge. The disappearance of the differences in tubular reabsorption during arginine and lysine infusion suggests that PGA isozymogens differ in affinity for negatively charged binding sites in the tubular cell membrane. In order to explain the low fractional clearance of PGC compared with that of PGA and the less marked effect of arginine or lysine infusion on the fractional clearance of PGC, an additional PGC-specific binding site has to be postulated.
Reassessment of the single intravenous injection method with inulin for measurement of the glomerular filtration rate in man
Authors: Prescott L. F. , Freestone S. , McAuslane J. A. N. 
Published: August 2015

1. Factors influencing the total body and renal clearances of inulin were investigated in a total of 37 healthy adult volunteers and 10 patients with stable chronic renal failure after the single intravenous injection of a dose of 70 mg/kg given over 5 min.
2. The elimination of inulin was highly concentration-dependent, and in healthy volunteers the renal clearance fell from 103.7 ± 14.4 ml min−1 1.73 m−2 during the first hour after administration to 49.1 ± 20.9 ml min−1 1.73 m−2 over the period 6-8 h. In the patients with renal failure the renal clearance fell correspondingly from 39.7 ± 16.5 to 26.6 ± 8.6 ml min−1 1.73 m−2. There were no changes in the simultaneously measured clearances of creatinine.
3. The values obtained for the total body clearance of inulin after a single injection depend critically on dose, the number and timing of blood samples, the choice of pharmacokinetic model, the number of data points chosen for estimation of the slope of the terminal elimination phase for analysis by the methods of residuals, and the weighting used for curve fitting by non-linear regression analysis.
4. With standardized conditions of sampling from 0 to 2 h and weighted non-linear regression analysis of the plasma concentration-time data, the total body and renal clearances of inulin were almost identical in subjects with normal renal function at 105.2 ± 10.2 and 102.9 ± 13.0 ml min−1 1.73 m−2. In the patients with chronic renal failure sampling was continued for 3 h and the corresponding clearances were 40.4 ± 15.3 and 38.9 ± 15.7 ml min−1 1.73 m−2.
5. The 0-2 h total body and renal clearances of inulin were measured by the single injection method and the renal clearance was measured by the standard constant infusion method on different occasions in 10 healthy volunteers. The respective clearances were similar at 101.4 ± 6.6, 94.9 ± 11.9 and 88.4 ± 12.1 ml min−1 1.73 m−2.
6. The reproducibility of the single injection and constant infusion methods was compared by measuring the inulin clearance with both techniques on three occasions in separate groups of eight and nine healthy volunteers. The mean coefficient of variation for the total body clearance with the single injection method was only 3.9% compared with 9.5% for the renal clearance determined the same way and 12.0% for the renal clearance during constant infusion.
7. Urine collection and fluid loading are not required for the single injection technique, and it is more reproducible and less demanding than the constant infusion method. With simple precautions, the single injection method with inulin is suitable for routine estimation of the glomerular filtration rate.
Orotidine Accumulation in Human Erythrocytes during Allopurinol Therapy: Association with High Urinary Oxypurinol-7-Riboside Concentrations in Renal Failure and in the Lesch-Nyhan Syndrome
Authors: Simmonds H. A. , Reiter S. , Davies P. M. , Cameron J. S. 
Published: August 2015

1. A compound identified as orotidine has been found in the erythrocytes of all subjects on allopurinol.
2. The erythrocyte orotidine concentrations were much higher in patients with renal failure or with the Lesch-Nyhan syndrome.
3. In addition, increased amounts of oxypurinol-7-riboside were excreted in the urine by both of these groups compared with control subjects or with patients with normal renal function on allopurinol.
4. A good correlation was found between urinary oxypurinol-7-riboside excretion and erythrocyte orotidine concentrations.
5. Increased erythrocyte levels of the pyrimidine-sugar UDP-glucose were also found in patients with the highest orotidine levels.
6. The combined results suggest a derangement of pyrimidine nucleotide metabolism during allopurinol therapy. We propose that erythrocyte orotidine formation results primarily from inhibition of orotidine-5′-mono-phosphate decarboxylase by oxypurinol-7-ribotide.
Renal and Cardiovascular Effects of Exogenous Insulin in Healthy Volunteers
Authors: Gans R. O. B. , v.d. Toorn L. , Bilo H. J. G. , Nauta J. J. P. , Heine R. J. , Donker A. J. M. 
Published: August 2015

1. Renal and cardiovascular effects of three dosages of insulin [50 (Ins I), 300 (Ins II) and 500 (Ins III) m-units h−1 kg−1] were investigated in healthy males by using a euglycaemic clamp technique. On separate days, control experiments were carried out to correct for any circadian variation in the variables studied.
2. All three insulin dosages resulted in a marked decline in fractional sodium excretion (actual experiments: basal, 0.95 ± 0.15%, Ins I, 0.79 ± 0.10%, Ins II, 0.80 ± 0.12%, Ins III, 0.84 ± 0.08%; control experiments: basal, 0.96 ± 0.10%, Ins I, 1.20 ± 0.12%, Ins II, 1.53 ± 0.15%, Ins III, 1.43 ± 0.10%; means ± sem, P &lt; 0.005, analysis of variance). With the highest insulin dosage, the reduction in fractional sodium excretion tended to be less striking. This coincided with a rise in heart rate, pulse pressure and pulse rate-systolic blood pressure product (double product). Although blood pressure itself did not change, systolic blood pressure also tended to increase (actual experiments: basal, 133 ± 5 mmHg, Ins I, 132 ± 5 mmHg, Ins II, 139 ± 5 mmHg, Ins III, 143 ± 4 mmHg; control experiments: basal, 128 ± 3 mmHg, Ins I, 129 ± 3 mmHg, Ins II, 130 ± 3 mmHg, Ins III, 133 ± 3 mmHg; means ± sem, P = 0.09, analysis of variance). There was a positive correlation between the change in fractional sodium excretion and the change in systolic blood pressure over control values (r = 0.696, P &lt; 0.028). At a rise in systolic blood pressure of 18 mmHg, the sodium-retaining effect of insulin appeared to be offset. A shift of the pressure-natriuresis relation to the right is suggested.
3. Plasma catecholamines did not change. Plasma renin activity increased from 1.11 ± 0.17 (basal) to 2.13 ± 0.31 (Ins III) pmol of angiotensin I h−1 ml−1; on the control day, a decline from 1.28 ± 0.24 (basal) to 0.81 ± 0.13 (Ins III) pmol of angiotensin I h−1 ml−1 was noted (P &lt; 0.001). Despite this rise no concomitant rise in plasma aldosterone occurred.
4. Chronic hyperinsulinaemia may lead to blood pressure elevation in the long-term if it is postulated that resistance to the glucose-lowering effect of insulin is absent for the effects of insulin on the kidney and the cardiovascular system.
Diurnal Blood Pressure Variation in Quadriplegic Chronic Spinal Cord Injury Patients
Authors: Krum Henry , Louis William J. , Brown Douglas J. , Jackman Graham P. , Howes Laurence G. 
Published: August 2015

1. Measurement of blood pressure and heart rate over a 24 h period was peformed in 10 quadriplegic spinal cord injury patients and 10 immobilized, neurologically intact orthopaedic subjects by using the Spacelabs 90207 automated ambulatory monitoring system.
2. Systolic and diastolic blood pressure fell significantly at night in orthopaedic subjects but not in quadriplegic patients, and night-time blood pressures were similar in both groups.
3. Cumulative summation of differences from a reference value (cusum analysis) confirmed a markedly diminished diurnal blood pressure variation in the quadriplegic patients.
4. These findings could not be accounted for on the basis of blood pressure variations during chronic postural change.
5. Heart rate fell significantly at night in both groups.
6. The findings suggest that the increase in blood pressure during waking hours in neurologically intact subjects is a consequence of a diurnal variation in sympathetic activity (absent in quadriplegic patients with sympathetic decentralization) which is independent of changes in physical activity.
Extent of pulmonary emphysema in man and its relation to the loss of elastic recoil
Authors: Gugger M. , Gould G. , Sudlow M. F. , Wraith P. K. , MaCnee W. 
Published: August 2015

1. We assessed lung density, determined by computerized tomography, as a measure of emphysema and related this to lung function and measurement of the elastic recoil of the lung in normal subjects and patients with chronic obstructive lung disease.
2. We found a significant correlation between measurements of elastic recoil pressure at 90% of total lung capacity and both the forced expiratory volume in 1 s (r = 0.80, P &lt;0.001) and the transfer factor for carbon monoxide (r = 0.70, P &lt;0.001). Measurements of elastic recoil of the lung also correlated with lung density as measured by computerized tomography scanning (P &lt;0.001).
3. Multiple regression analysis demonstrated a correlation between the density of the lowest fifth percentile of the computerized tomography lung-density histogram, and both the natural logarithm of the shape parameter of the pressure-volume curve (P &lt;0.01), and the transfer factor for carbon monoxide (P &lt;0.01). However, the mean computerized tomography lung density correlated, in addition, with the elastic recoil pressure of the lungs at 90% of total lung capacity (P &lt;0.001).
4. Since the elastic recoil pressure correlates with computerized tomography lung density, and hence with emphysema, and since elastic recoil pressure also correlates with the forced expiratory volume in 1 s, these results suggest that loss of elastic recoil is one determinant of airflow limitation in patients with chronic obstructive lung disease.
Hypothalamic regulatory peptides in obese and lean Zucker rats
Authors: Williams Gareth , Cardoso Helena M. , Lee Ying C. , Ball Joanna M. , Ghatei Mohammad A. , Stock Michael J. , Bloom Stephen R. 
Published: August 2015

1. Hypothalamic concentrations of nine peptides with experimental effects on energy balance were compared in obese (fa/fa) and lean (Fa/?) male Zucker rats. To determine whether any peptide differences between obese and lean rats might be due to the overweight condition per se, separate groups of obese rats were food-restricted to reduce their body weight to lean values.
2. Concentrations of neuromedin B, a bombesin-like peptide, in the central hypothalamus were significantly higher in obese than in lean rats. This difference was not affected in food-restricted obese rats.
3. Hypothalamic levels of neuropeptide Y, an extremely potent central appetite stimulant, were similar in lean and freely fed obese rats but central hypothalamic levels of neuropeptide Y rose significantly in food-restricted obese rats.
4. These findings suggest that disturbances in hypothalamic neuromedin B concentrations may be involved in the obesity syndrome of the fa/fa Zucker rat. Increased central hypothalamic levels of neuropeptide Y in food-restricted rats suggest that this peptide may help to defend body weight by stimulating eating after weight loss.
Role of prostaglandins in the natriuresis of head-out water immersion in humans
Authors: Rabelink Ton J. , Koomans Hein A. , Mees Evert J. Dorhout 
Published: August 2015

1. Prostaglandins may play a role in the natriuresis seen after acute circulatory challenges. To assess this role in head-out water immersion, we compared, in clearance studies, the effects of acute (24 h) and chronic (7 days) administration of indomethacin, an inhibitor of prostaglandin synthesis, on the renal response to head-out water immersion in six healthy subjects on a 200 mmol of sodium/day diet and on a 40 mmol of sodium/day diet.
2. Indomethacin caused a similar degree of sodium retention on each of these two diets.
3. During the 40 mmol of sodium/day diet, acute administration of indomethacin decreased sodium excretion before, as well as during, head-out water immersion; however, the relative increase caused by head-out water immersion was normal. After chronic administration of indomethacin, both baseline sodium excretion and the natriuresis induced by head-out water immersion were similar to those in control studies.
4. During the 200 mmol of sodium/day diet, indomethacin had no effect on baseline sodium excretion, nor on the natriuretic effect of head-out water immersion.
5. Head-out water immersion decreased tubular lithium reabsorption and increased diluting segment delivery. Despite opposite effects of indomethacin on these parameters, indomethacin did not prevent the tubular effects of head-out water immersion on either diet. However, indomethacin did prevent the marked increase in estimated renal plasma flow and the fall in filtration fraction that were observed during head-out water immersion in the absence of indomethacin (control).
6. Head-out water immersion was not associated with an increase in urinary excretion of prostaglandins. Indomethacin lowered baseline urinary excretion of prostaglandins, which did not change further during head-out water immersion.
7. We therefore conclude that renal prostaglandins are not essential for a normal natriuretic response to head-out water immersion, although they may mediate the vasodilatation induced by head-out water immersion.
Enhanced urinary excretion of leukotriene E4 by patients with multiple trauma with or without adult respiratory distress syndrome
Authors: Fauler Joachim , Tsikas Dimitrios , Holch Michael , Seekamp Andreas , Nerlich Michael L. , Sturm Johannes , Frölich Jürgen C. 
Published: August 2015

1. The aim of the present study was to evaluate the systemic synthesis of cysteinyl leukotrienes in patients with multiple trauma. In order to do this, the urinary excretion of leukotriene E4 was assessed in the first 10 days after trauma.
2. Leukotriene E4 was unequivocally identified by g.c.-m.s. in the urine of healthy subjects and patients with multiple trauma after its conversion to 5-hydroxyeicosanoic acid. Leukotriene E4 was routinely isolated from 24 h urine samples by solid-phase extraction followed by reverse-phase h.p.l.c. and was subsequently quantified by r.i.a.
3. Healthy subjects excreted daily 10 ± 3 nmol of leukotriene E4/mol of creatinine (mean ± sem, n = 16) into urine.
4. Patients with multiple trauma who did not develop adult respiratory distress syndrome (n = 7) excreted 76.8 ± 6.7 nmol of leukotriene E4/mol of creatinine (mean ± sem) daily during the first 10 days after trauma, which was significantly (P &lt; 0.01) more than did healthy subjects.
5. Excretion of leukotriene E4 was even more enhanced in three patients with multiple trauma who developed adult respiratory distress syndrome. Maximal amounts of 593 ± 185 nmol of leukotriene E4/mol of creatinine (mean ± sem) were excreted on day 9 after trauma by these three patients, which corresponds to a 7.7- and a 59-fold increase in excretion of leukotriene E4 compared with patients with multiple trauma who did not develop adult respiratory distress syndrome and healthy subjects, respectively.
6. The present study demonstrates an enhanced synthesis of cysteinyl leukotrienes in patients with multiple trauma, and suggests that cysteinyl leukotrienes are involved in the inflammatory reaction that follows multiple trauma.
Glutamine metabolism in the lungs of glucocorticoid-treated rats
Authors: Salleh M. , Ardawi M. 
Published: August 2015

1. The effect of dexamethasone (30 μg day−1 100 g−1 body weight) on the regulation of glutamine metabolism was studied in the lungs of rats after 9 days of treatment.
2. Dexamethasone resulted in a negative nitrogen balance, and produced decreases in the blood concentrations of glutamine (32.3%) and glutamate (25.3%) but an increase in the blood concentration of alanine (33.9%).
3. Dexamethasone treatment increases the rates of production of glutamine and alanine by lung slices incubated in vitro.
4. Blood flow and arteriovenous concentration difference measurement across the lungs exhibited an increase in the net exchange rates of glutamine (131.6%) and alanine (113.2%) in dexamethasone-treated rats compared with corresponding pair-fed controls.
5. Dexamethasone treatment produced significant decreases in the lung concentrations of glutamine (47.2%), glutamate (30.9%) and 2-oxoglutarate (57.3%). The concentrations of alanine (52.1%), ammonia (24.7%) and pyruvate (43.7%) were increased.
6. The maximal activity of glutamine synthetase was increased (21.5%), but there was no marked change in that of glutaminase, in the lungs of dexamethasone-treated rats.
7. It is concluded that glucocorticoid administration enhances the rates of production of glutamine and alanine from lungs of rats (both in vitro and in vivo). This may be due to changes in efflux and/or increased intracellular biosynthesis of glutamine and alanine.
Renal haemodynamics of cyclosporin A nephrotoxicity in children with juvenile dermatomyositis
Authors: Peters A. M. , Heckmatt J. Z. , Hasson N. , Henderson B. L. , EL-Meleigy D. , Rose M. L. , Dubowitz V. 
Published: August 2015

1. Renal haemodynamics were monitored over an average period of 19 months in 17 children being treated with cyclosporin A. Sixteen had juvenile dermatomyositis and one had chronic polyneuropathy. The dose of cyclosporin A ranged from 2.3 to 8.3 mg day−1 kg−1 (median 4.1 mg day−1 kg−1).
2. Glomerular filtration rate (expressed in terms of extracellular fluid volume), renal blood flow (expressed as a fraction of cardiac output) and filtration fraction were measured by using 99mTc-labelled diethylenetriaminepenta-acetate. They were compared with the dosage and trough blood levels of cyclosporin A, and, in 15 patients receiving prednisolone in addition to cyclosporin A, with steroid dosage.
3. All 17 children had a renogram performed 6 months after starting cyclosporin A treatment. Nine of them also had a renogram before starting cyclosporin A treatment (baseline study), while 13, in addition to their renogram 6 months after starting cyclosporin A treatment, also had at least one further renogram.
4. Glomerular filtration rate/extracellular fluid volume fell slightly but significantly from 0.009 (sd 0.0013) before starting cyclosporin A treatment to 0.0085 (0.002) min−1 (P &lt; 0.01) 6 months after cyclosporin A treatment in the nine children who underwent a baseline study. This was accompanied by a significant (P &lt; 0.001) fall in filtration fraction from 0.108 (0.015) to 0.088 (0.014). However, renal blood flow/cardiac output showed no change.
5. In the 13 children studied beyond 6 months after starting cyclosporin A treatment, there was no further significant overall change in any renal haemodynamic variable. However, throughout this period, trough blood levels of cyclosporin A, which ranged from 20 to 258 ng/ml (median 67 ng/ml), correlated inversely with glomerular filtration rate/extracellular fluid volume, but not with renal blood flow/cardiac output. Furthermore, although a weak correlation between filtration fraction and trough blood levels of cyclosporin A did not reach statistical significance, sequential changes in filtration fraction correlated significantly with corresponding sequential changes in glomerular filtration rate/extracellular fluid volume.
6. We conclude that the predominant mechanism of renal impairment at these relatively low trough blood levels of cyclosporin A is a reversible reduction in filtration fraction.
Fasting and post-prandial splanchnic blood flow is reduced by a somatostatin analogue (octreotide) in man
Authors: Cooper A. M. , Braatvedt G. D. , Qamar M. I. , Brown H. , Thomas D. M. , Halliwell M. , Read A. E. , Corrall R. J. M. 
Published: August 2015

1. The effects of the subcutaneous administration of a long-acting somatostatin analogue (octreotide) or of placebo on the splanchnic blood flow response to a mixed solid meal has been examined in eight normal subjects by using a transcutaneous Doppler ultrasound technique. Each subject was studied on two occasions more than 1 week apart.
2. On the control day, feeding had a pronounced effect on both superior mesenteric artery and portal venous blood flows, causing a peak rise of 82% in superior mesenteric artery blood flow at 15 min and of 75% in portal venous blood flow at 30 min post-prandially (P &lt; 0.001). Blood flows remained elevated 2 h after the meal. Pulse and blood pressure showed no significant changes from baseline.
3. Octreotide reduced fasting superior mesenteric artery blood flow by 59% (P &lt; 0.05) and portal venous blood flow by 49% (P &lt; 0.01) and blunted the normal post-prandial rise. Pulse and blood pressure did not change in response to either the injection or the ingestion of the meal.
4. Octreotide suppressed the release of insulin, glucagon and pancreatic polypeptide in response to feeding and resulted in post-prandial hyperglycaemia.
5. The mechanism of action of octreotide on splanchnic blood flow is uncertain. It may be mediated via a direct vascular effect or it may act via suppression of vasoactive intestinal hormones.