bluuebunny/crossref_metadata_2025_split huggingface dataset:
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 &lt; 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 &lt; 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.
Polymorphisms in the Gene Coding for Cholesteryl Ester Transfer Protein are Related to Plasma High-Density Lipoprotein Cholesterol and Transfer Protein Activity
Authors: Freeman Dilys J. , Packard Christopher J. , Shepherd James , Gaffney Dairena 
Published: August 2015

1. Cholesteryl ester transfer protein activity may have a physiological effect on high-density lipoprotein levels.
2. We examined restriction fragment length polymorphisms associated with the cholesteryl ester transfer protein gene and the apolipoprotein AI gene in a group of 60 unrelated subjects selected from an initial survey of 5000 subjects on the basis of their high-density lipoprotein levels being high or low at the extremes of the distribution. The activities of cholesteryl ester transfer protein and lectithin:cholesterol acyltransferase (phosphatidylcholine-sterol acyltransferase, EC 2.3.1.43) were also determined. Analysis by selection of those with a low high-density lipoprotein cholesterol level (≤ 1.1 for males, ≤ 1.2 for females) gave 32 individuals with 24% B2 alleles. Selection of subjects with a high-density lipoprotein cholesterol level (≥ 2 mmol/l) gave 17 with 62% B2 alleles.
3. The group with low levels of high-density lipoprotein cholesterol had higher activity of cholesteryl ester transfer protein and significantly elevated triacylglycerol levels when compared with the group with high levels of high-density lipoprotein cholesterol.
4. A further significant finding was the correlation of the Msp1 restriction fragment length polymorphism detected by the apolipoprotein AI gene with lecithin:cholesterol acyltransferase activity.
Effect of Polycations on the Function of the Isolated Perfused Rat Kidney
Authors: Firth J. D. 
Published: August 2015

1. In minimal change nephrotic syndrome the occurrence of heavy proteinuria can be explained on the basis of a reduction in charge selectivity of the glomerular filtration barrier, and it has been proposed that this might be caused by the neutralization of anionic groups by a circulating polycationic factor.
2. The effects of two polycations, protamine and poly-l-lysine, on the function of the isolated perfused rat kidney have been examined.
3. Poly-l-lysine polymers of relatively high molecular weight (8800 and 17800) induced heavy proteinuria, while simultaneously causing a marked increase in renal vascular resistance and a fall in filtration rate. Protamine (approximate molecular weight 7000) at relatively high concentration induced modest proteinuria in the absence of effects on vascular resistance or filtration rate.
4. A poly-l-lysine polymer of lower molecular weight (3800) did not induce proteinuria. Protamine at a concentration of 40 μg/ml and below did not affect protein excretion either. Both provoked substantial natriuresis. This appeared to be largely due to an effect on the tubular handling of sodium since the filtration rate remained steady while fractional sodium excretion rose markedly.
5. The natriuretic effect of protamine was blocked by heparin, but not by indomethacin or verapamil, suggesting that the mechanism of natriuresis did not depend upon either prostaglandin production or entry of calcium through verapamil-sensitive channels.
Dynamic Association between Artery Shear flow Condition and Platelet Cytosolic Free Ca2+ Concentration in Human Hypertension
Authors: Levenson Jaime , Devynck Marie-Aude , Pithois-Merli Isabelle , Le Quan Sang Kim Hanh , Filitti Vincenzo , Simon Alain 
Published: August 2015

1. Blood cells and vascular endothelial cells are subjected to a wide range of haemodynamically generated shear stress forces. In vitro, membrane stretching or shear stress have been observed to activate ion channels and cell metabolism and to facilitate erythrocyte and platelet aggregation.
2. The present study was designed to evaluate the participation of shear stresses in the control of apparent platelet cytosolic free Ca2+ concentration in hypertensive patients.
3. Shear conditions and platelet cytosolic free Ca2+ concentration in vitro were studied after a dynamic perturbation induced by 3 months of double-blind treatment with one of two β-antagonists, carteolol and atenolol. Brachial artery wall shear rate and stress were estimated by means of a pulsed Doppler velocimeter, and blood viscosity was measured by a co-axial viscometer at a shear rate of 96 s−1. Platelet cytosolic free Ca2+ concentration was simultaneously measured by using the Quin-2 fluorescent chelator. The direct effect of atenolol and carteolol on platelet cytosolic free Ca2+ concentration in vitro was also measured after addition of the β-blockers to plateletrich plasma.
4. Atenolol and carteolol decreased blood pressure similarly but their effects on shear rate (P &lt; 0.02), shear stress (P &lt; 0.01) and platelet cytosolic free Ca2+ concentration (P &lt; 0.05) differed after 3 months of therapy. In contrast, neither of the drugs significantly altered platelet cytosolic free Ca2+ concentration, in vitro per se.
5. In the overall population, strong positive correlations existed not only between changes in platelet cytosolic free Ca2+ concentration and those in shear rate (r = 0.81, P &lt; 0.001) and shear stress (r = 0.83, P &lt; 0.001), but also between their absolute values, suggesting a possible haemodynamic shear-dependent modulation of transmembrane Ca2+ transport.
Cardiovascular reflex responses in Bangladeshi and European subjects
Authors: Rahman M. A. , Farquhar I. , Bennett T. 
Published: August 2015

1. Cardiovascular responses to three different interventions, namely the Valsalva manoeuvre, deep breathing and a cold stimulus on the face, were studied in two ethnic groups (European and Bangladeshi) that have been shown to differ in the prevalence of hypertensive-vascular disease. The data obtained consisted of systolic blood pressure, diastolic blood pressure, mean blood pressure, heart rate measured by using a beat-by-beat non-invasive blood pressure monitor (the Finapres), forearm blood flow determined by venous occlusion plethysmography, and calculated forearm vascular resistance.
2. The resting haemodynamic status was similar in European and Bangladeshi subjects. However, Bangladeshi subjects showed a greater increase in heart rate, but only after 20 s into the Valsalva manoeuvre, and greater overshoots in mean blood pressure after the manoeuvre than the European subjects. Furthermore, after cold face stimulation the fall in forearm vascular resistance to baseline levels was delayed in Bangladeshi subjects relative to that in the European subjects.
3. There were no inter-group differences in the reflex bradycardia relative to mean blood pressure or in the cardiac baroreflex sensitivity estimated from systolic blood pressure and pulse interval after the Valsalva manoeuvre. In addition, values for the mean difference between maximum and minimum pulse intervals during deep breathing did not differ in Bangladeshi and European subjects.
4. These findings together suggest that, although cardiac vagal reflex responses appear similar in the two groups, sympatho-adrenal influences on the heart and vasculature may be greater in Bangladeshi subjects than in European subjects.
Abnormal renal glucose handling in X-linked hypophosphataemic mice
Authors: Mühlbauer R. C. , Fleisch H. 
Published: August 2015

1. The renal handling of glucose was determined in male X-linked hypophosphataemic (Hyp/Y) mice and in control littermates (+/Y) aged 4 months. Plasma glucose concentration and urinary glucose excretion were measured before and during stepwise increase in glycaemia induced by an acute infusion of glucose. The relationship between plasma glucose concentration and urinary glucose excretion was monitored per ml of glomerular filtrate in mice fed high and low phosphate diets.
2. Hyp/Y mice fed the high phosphate diet showed a significantly higher glucosuria compared with +/Y littermates. When glycaemia was increased, Hyp/Y mice developed frank glucosuria earlier than +/Y animals. In Hyp/Y mice we could not find a threshold below which virtually no glucose was excreted in the urine, whereas this was clearly visible in +/Y mice. These differences persisted in animals fed the low phosphate diet.
3. Using the acute response to the glucoregulatory hormones, glucagon and insulin, administered exogenously, we found that the regulation of plasma glucose concentration did not differ between Hyp/Y and +/Y mice.
4. The significantly lower plasma glucose concentration observed in Hyp/Y as compared with +/Y mice decreased further during fasting.
5. We conclude that the renal reabsorptive capacity for glucose is defective in Hyp/Y mice and their low plasma glucose concentration may be explained by the renal leak. Therefore the X-linked phosphataemic mouse appears not only to be characterized by a defect in renal phosphate and calcium reabsorption but also by an altered glucose reabsorption.
Abnormal erythrocyte choline transport in patients with chronic renal failure
Authors: Fervenza F. C. , Meredith D. , Ellory J. C. , Hendry B. M. 
Published: August 2015

1. Erythrocyte choline transport has been studied in nine patients on maintenance haemodialysis for chronic renal failure, six patients on continuous ambulatory peritoneal dialysis, 31 patients with renal transplants and in nine normal control subjects.
2. The mean maximum rate of choline influx (Vmax., measured at an extracellular choline concentration of 250 μmol/l) was 66.7 (sd 14.1) μmol h−1 l−1 cells in patients on haemodialysis, 87.8 (sd 18.5) μmol h−1 l−1 cells in patients on continuous ambulatory peritoneal dialysis and 30.5 (sd 4.9) μmol h−1 l−1 cells in control subjects. The increase in choline flux in patients on haemodialysis and patients on continuous ambulatory peritoneal dialysis compared with control subjects was highly significant (P &lt; 0.001).
3. Renal transplant patients showed variable values for the Vmax. of choline influx (range 17.7-71.7 μmol h−1 l−1 cells). The values showed a signifcant negative correlation with creatinine clearance and this correlation correctly extrapolated to the maximum choline flux in normal subjects and in patients on dialysis.
4. The kinetics of choline transport have been studied in erythrocytes of patients on haemodialysis and control subjects in ‘zero-trans’ conditions after depletion of intracellular choline. The mean Vmax. in these conditions was 38.4 (sd 4.6) μmol h−1 l−1 cells in patients on haemodialysis compared with 14.2 (sd 3.7) μmol h−1 l−1 cells in control subjects. The mean Km under ‘zero-trans’ conditions was 19.4 (sd 2.4) μmol/l in patients on haemodialysis and 7.4 (sd 1.4) μmol/l in control subjects. These differences were significant (P &lt; 0.001).
Oral carbidopa has no effect on the renal response to angiotensin II in normal man
Authors: Eadington D. W. , Swainson C. P. , Lee M. R. 
Published: August 2015

1. The effect of inhibition of intrarenal dopamine synthesis by carbidopa on the renal response to angiotensin II infusion was studied in six healthy salt-loaded volunteers.
2. Subjects received an infusion of angiotensin II at two doses (0.5 and 1.0 ng min−1 kg−1) on two occasions. Before one study they took a single dose of carbidopa (100 mg) by mouth.
3. The plasma concentrations of angiotensin II produced by the infusion were similar on both study days. Angiotensin II infusion reduced urinary dopamine excretion on the control day. Urinary dopamine excretion was undetectable at all times after carbidopa, but carbidopa did not change the basal excretion rate of sodium. Despite inhibition of renal dopamine synthesis, the reductions in both absolute and fractional sodium excretion during the angiotensin II infusion were not different from those seen in the control study.
4. The reductions in glomerular filtration rate and effective renal plasma flow which occurred during angiotensin II infusion were not modified by pretreatment with carbidopa.
5. The renal response to angiotensin II is not modulated either wholly or in part by endogenous intrarenal dopamine levels. The fall in urinary dopamine excretion which occurs during angiotensin II infusion is consistent with a modulatory role for tubular reabsorptive capacity in the regulation of proximal tubular dopamine synthesis.
Indocyanine Green elimination in patients with liver disease and in normal subjects
Authors: Burns E. , Triger D. R. , Tucker G. T. , Bax N. D. S. 
Published: August 2015

1. The validity of a two-compartment pharmacokinetic model for the estimation of the hepatic extraction ratio of Indocyanine Green was tested in six patients with cirrhosis of the liver.
2. No agreement was found between the value of the hepatic extraction ratio measured directly and that calculated using the two-compartment model.
3. To investigate the reasons for the failure of the model, an extended sampling period was used to define the time course of Indocyanine Green in plasma in six healthy subjects and in six patients with cirrhosis of the liver after a bolus injection of the dye.
4. Indocyanine Green was measurable in the plasma for up to 10 h after injection in healthy subjects, and up to 48 h after injection in the patients. The plasma elimination curve in both groups was best described by a triexponential function.
5. The clearance of Indocyanine Green calculated using data collected in the first 20 min after injection overestimated that calculated using data collected for as long as Indocyanine Green was measurable in the plasma. In the patients with cirrhosis the mean overestimate was 87%.
6. Thus, a two-compartment pharmacokinetic model was inappropriate for the description of the disposition of Indocyanine Green and estimates of the hepatic extraction ratio obtained using this model in patients with cirrhosis were inaccurate.
Neuronal Re-Uptake of Noradrenaline by Sympathetic Nerves in Humans
Authors: Eisenhofer Graeme , Esler Murray D. , Meredith Ian T. , Ferrier Claudia , Lambert Gavin , Jennings Garry 
Published: August 2015

1. Plasma concentrations of [3H]dihydroxyphenylglycol, the intraneuronal metabolite of noradrenaline, were examined during intravenous infusion of [3H]noradrenaline in 43 subjects, to assess the nature of its formation. Noradrenaline re-uptake by sympathetic nerves was estimated in 11 subjects from the effects of neuronal uptake blockade with desipramine on noradrenaline clearance and plasma concentrations of [3H]dihydroxyphenylglycol and endogenous dihydroxyphenylglycol. In seven subjects noradrenaline re-uptake and spillover into plasma were examined before and during mental arithmetic or handgrip exercise.
2. During infusion of [3H]noradrenaline, plasma [3H]dihydroxyphenylglycol increased progressively, indicating its formation from previously stored [3H]noradrenaline leaking from vesicles as well as from [3H]noradrenaline metabolism immediately after removal into sympathetic nerves. Thus, to estimate noradrenaline reuptake, the amount of [3H]dihydroxyphenylglycol derived from [3H]noradrenaline metabolized immediately after removal into the sympathetic axoplasm must be isolated from that derived from [3H]noradrenaline sequestered into vesicles.
3. At rest in the supine position the rate of noradrenaline re-uptake was 474 ± 122 pmol min−1 kg−1, 9.5-fold higher than the rate of spillover of noradrenaline into plasma (49.6 ± 6.4 pmol min−1 kg−1). Noradrenaline reuptake and spillover into plasma were both increased during mental arithmetic and isometric handgrip exercise.
Inhibition of Neutral Endopeptidase (EC 3.4.24.11) Leads to An Atrial Natriuretic Factor-Mediated Natriuretic, Diuretic and Antihypertensive Response in Rodents
Authors: Shepperson N. B. , Barclay P. L. , Bennett J. A. , Samuels G. M. R. 
Published: August 2015

1. Atrial natriuretic factor is metabolized by neutral endopeptidase (atriopeptidase; EC 3.4.24.11) in vitro. Inhibitors of this enzyme have been reported to prolong the half-life of atrial natriuretic factor in vivo and to potentiate the renal and haemodynamic effects of exogenous atrial natriuretic factor.
2. (±)-Candoxatrilat, a selective neutral endopeptidase inhibitor, potentiated the natriuretic and diuretic response to volume loading in anaesthetized rats. Part of the response to volume loading and the potentiation by (±)-candoxatrilat was prevented by a polyclonal atrial natriuretic factor antiserum. The diuretic and natriuretic responses evoked by hydrochlorothiazide were not altered by the antiserum.
3. (±)-Candoxatrilat reduced systolic blood pressure of one-kidney deoxycorticosterone acetate-salt hypertensive rats for over 5 h. This response was abolished by pretreatment with atrial natriuretic factor antiserum.
4. These data demonstrate that the neutral endopeptidase inhibitor (±)-candoxatrilat has natriuretic/diuretic and antihypertensive effects in rodents, and that these effects are mediated via endogenous atrial natriuretic factor.
How important are suppression of aldosterone and stimulation of atrial natriuretic peptide secretion in the natriuretic response to an acute sodium load in man?
Authors: Singer D. R. J. , Shirley D. G. , Markandu N. D. , Miller M. A. , Buckley M. G. , Sugden A. L. , Sagnella G. A. , MacGregor G. A. 
Published: August 2015

1. Aldosterone is suppressed by sodium loading. We studied the contribution of this decrease in plasma aldosterone to the natriuresis after acute sodium loading in healthy volunteers.
2. Two litres of saline [0.9% (w/v) NaCl] were infused during the second hour of a 6 h infusion of aldosterone (3 pmol min−1 kg−1) or placebo in eight healthy young men. On the placebo day, plasma aldosterone decreased by 30 min after the start of saline infusion and remained suppressed. During aldosterone infusion, plasma aldosterone was maintained at around 400 pmol/l.
3. Urinary sodium excretion, lithium clearance and plasma atrial natriuretic peptide increased and plasma renin activity decreased after saline infusion, whether or not aldosterone was infused. However, from 60 to 240 min after saline infusion, natriuresis was significantly less during aldosterone infusion than on the placebo day. In addition, saline loading led to a progressive increase in the ratio of sodium clearance to lithium clearance, used as an index of the fractional distal tubular rejection of sodium, and in the ratio of urinary sodium to potassium. These increases were prevented by the infusion of aldosterone.
4. This study suggests that there are differences in the mechanisms determining the early and the later responses to an acute sodium load. Suppression of aldosterone may explain much of the later increase in natriuresis after saline infusion. In addition, the results are consistent with a role for atrial natriuretic peptide in the immediate increase in sodium excretion after saline loading.
Triacylglycerol in the human erythrocyte: quantification and fatty acyl turnover in normal subjects and chronic alcoholics
Authors: Lerique Brice , Gastaldi Marguerite , Boyer Jean 
Published: August 2015

1. Triacylglycerol in erythrocytes from normal human subjects was estimated to average 2.7 ± 0.7 nmol/1010 cells, equivalent to 0.07% of total lipids or 0.3% of neutral lipids.
2. The specific activity of triacylglycerol labelling attained by incubating intact erythrocytes with [3H]oleic acid was 10 nmol/μmol, a value 20-fold higher than that of the highest labelled phospholipid, sphingomyelin; as isolated by ultracentrifugation over a density gradient, the youngest erythrocytes exhibited a labelling rate 10-fold higher than that of older cells.
3. The triacylglycerol content was not modified in erythrocytes from chronic alcoholics, whereas the mean rate of triacylglycerol labelling was 31% (P &lt;0.05) higher than that of control subjects, and did not normalize 4 weeks after alcohol withdrawal.
4. These results indicate that triacylglycerol, although a quantitatively minor component, is one of the most active metabolites in the lipid matrix of the human erythrocyte membrane and appears to be implicated in the membrane response to antagonistic agents.