bluuebunny/crossref_metadata_2025_split huggingface dataset:
Endothelium-Dependent Modulation of Responses to Endothelin-1 in Human Veins
Authors: Haynes William G. , Webb David J. 
Published: August 2015

1. We have investigated whether local vascular production of nitric oxide or prostacyclin regulates venoconstriction induced by the endothelium-derived peptide, endothelin-1, in vivo in man.
2. Six healthy subjects received local dorsal hand vein infusion of endothelin-1 for 60 min alone or, on two separate occasions, co-infused with the donator of nitric oxide, glyceryl trinitrate, or the vasodilator prostaglandin, prostacyclin. In further studies, endothelin-l was co-infused with an inhibitor of nitric oxide production, NG-monomethyl-L-arginine, or after oral administration of the irreversible inhibitor of prostaglandin production, acetylsalicylic acid (aspirin).
3. At a low dose (5 pmol/min), endothelin-1 alone caused slowly developing and long-lasting venoconstriction (maximal constriction: 66 ± 4%). Although glyceryl trinitrate partially prevented endothelin-1-induced venoconstriction (maximum: 33 ± 5%), inhibition of nitric oxide production did not affect endothelin-1-induced venoconstriction (maximum: 55 ± 4%).
4. Prostacyclin was more effective at blocking the venoconstriction in response to endothelin-1 than glyceryl trinitrate (maximum: 12 ± 3%), and there was substantial potentiation of endothelin-1-induced venoconstriction after pretreatment with aspirin (maximum: 90 ± 3%).
5. Despite the capacity of nitric oxide to attenuate responses to endothelin-1, NG-monomethyl-L-arginine did not potentiate endothelin-1-induced venoconstriction, suggesting little or no stimulated production of nitric oxide in human veins. However, the potentiation of responses to endothelin-1 by aspirin indicates that endothelial production of prostacyclin attenuates responses to endothelin-1 in human veins in vivo.
Long-Term Insulin Treatment of Vascular Smooth Muscle Cells from Rat Aorta Attenuates the Synergistic Effect of Insulin on Angiotensin II- and Epidermal Growth Factor-Induced DNA Synthesis
Authors: Yon KO , Nettekoven Willy , Christian Roger , Wieczorek Andreas J. , Düsing Rainer , Vetter Hans , Sachinidis Agapios 
Published: August 2015

1. in the present study the effects of acute and chronic insulin treatment on growth factor-induced cell growth were investigated in vascular smooth muscle cells. Cell growth was quantified by the incorporation of [3H]thymidine into cell DNA and by determination of total protein.
2. Insulin in a concentration range of 10−9-10−6 mol/l had no effect on cell DNA synthesis. Insulin-like growth factor-1 in a concentration range of 10−9-10−6 mol/l induced a concentration-dependent increase in total cell protein, whereas no changes in DNA synthesis were observed.
3. Acutely, insulin enhanced the mitogenic effect of epidermal growth factor and angiotensin II. Long-term treatment with 10 and 100 ng/ml insulin over 14 weeks was associated with a time-dependent reduction in this potentiating effect of insulin on growth factor-induced DNA synthesis. To evaluate the mechanism of this effect, receptor binding studies were performed with 125I-labelled insulin-like growth factor-1. No difference in the Kd value (2.1 nmol/l) for insulin-like growth factor-1 was found between untreated and chronically insulin-treated cells, whereas the maximal number of binding sites decreased from 5.9 × 104 (untreated cells) to 4.7 × 104 (10 ng/ml) and to 4.3 × 104 (100 ng/ml) binding sites/cell in chronically insulin-treated cells.
4. We conclude that insulin acutely enhances the mitogenic effect of various growth factors such as epidermal growth factor and angiotensin II on vascular smooth muscle cells. Long-term insulin treatment reduced the number of receptor binding sites for insulin-like growth factor-1. This may contribute to the reduced response of cells to growth stimulation after chronic in contrast with acute insulin treatment.
Treatment of Anaemia in Haemodialysis Patients with Erythropoietin: Long-Term Effects on Exercise Capacity
Authors: Báaráany Peter , Freyschuss Ulla , Pettersson Erna , Bergström Jonas 
Published: August 2015

1. The effects of correcting anaemia on exercise capacity were evaluated in 21 haemodialysis patients (aged 39 ± 12 years) before starting treatment with recombinant human erythropoietin (Hb concentration, 73 ± 10 g/l; total Hb, 59 ± 12% of expected), after correction of the anaemia to a Hb concentration of 108 ± 7 g/l and a total Hb 82 ± 10% of expected, and in 13 of the patients after 12 months on maintenance recombinant human erythropoietin treatment (Hb concentration 104 ± 14 g/l, total Hb 79 ± 17% of expected). Fifteen healthy subjects (aged 41 ± 9 years), who took no regular exercise, constituted the control group. Maximal exercise capacity was determined on a bicycle ergometer. Oxygen uptake, respiratory quotient, blood lactate concentration, heart rate and blood pressure were measured at rest and at maximal workload.
2. After 6 ± 3 months on recombinant human erythropoietin, maximal exercise capacity increased from 108 ± 27 W to 130 ± 36 W (P &lt; 0.001) and the maximal oxygen uptake increased from 1.24 ± 0.39 litres/min to 1.50 ± 0.45 litres/min (P &lt; 0.001). No significant changes in respiratory quotient (1.16 ± 0.13 versus 1.18 ± 0.13) and blood lactate concentration (4.0 ± 1.8 versus 3.6 ± 1.1 mmol/l) at maximal workload were observed, but the blood lactate concentration in the patients was significantly lower than that in the control subjects (6.7 ± 2.3 mmol/l, P &lt; 0.01). After the correction of anaemia, the aerobic power was still 38% lower in the patients than in the control subjects and 17% lower than the reference values.
3. After 12 months on maintenance recombinant human erythropoietin treatment (17 ± 3 months from the start of the study), no further significant changes were observed in maximal exercise capacity (before start, 112 ± 31 W, 6 ± 3 months, 134 ± 42 W, 17 ± 3 months, 134 ± 50 W), maximal oxygen uptake (before start, 1.33 ± 0.45 litres/min; 6 ± 3 months, 1.59 ± 0.54 litres/min; 17 ± 3 months, 1.75 ± 0.78 litres/min) or blood lactate concentration (before start, 4.4 ± 1.9 mmol/l; 6 ± 3 months, 4.0 ± 1.0 mmol/l; 17 ± 3 months, 4.7 ± 2.0 mmol/l).
4. Thus, in haemodialysis patients the improvement in maximal aerobic power after the correction of anaemia persists without marked changes during long-term treatment with recombinant human erythropoietin. We did not observe any effects on exercise capacity that could be attributed to a spontaneous increase in physical activity after treatment of anaemia.
Sialic Acids in Human Gastric Aspirates: Detection of 9-O-Lactyl- and 9-O-Acetyl-N-Acetylneuraminic Acids and a Decrease in Total Sialic Acid Concentration with Age
Authors: Corfield A. P. , Wagner S. A. , Safe A. , Mountford R. A. , Clamp J. R. , Kamerling J. P. , Vliegenthart J. F. G. , Schauer R. 
Published: August 2015

1. The total sialic acid content of human gastric aspirates was measured using a colorimetric assay. Care was taken to optimize the assay and to eliminate interference.
2. The sialic acid content of gastric aspirates collected under resting conditions from 77 patients with non-ulcer dyspepsia was found to decrease with age from &gt;100 μg/ml at 25 years and younger to &lt;20 μg/ml above 70 years of age.
3. Analysis of the sialic acids by gas chromatography, mass spectrometry and thin-layer chromatography showed the presence of N-acetylneuraminic acid and two O-acylated derivatives, 9-O-acetyl- and 9-O-lactyl-N-acetylneuraminic acids. These forms were predominantly glycosidically bound.
4. Thin-layer chromatographic analysis of individual aspirate samples showed that the O-acetylated sialic acids were present in all samples, with a maximum of 25% and a minimum of 5% of the total sialic acids.
Glycated Albumin in Serum and Dialysate of Patients on Continuous Ambulatory Peritoneal Dialysis
Authors: Lamb E. , Cattell W. R. , Dawnay A. 
Published: August 2015

1. Chronic use of hyperosmolar glucose solutions in continuous ambulatory peritoneal dialysis may cause glycation of peritoneal structural proteins which could contribute to membrane dysfunction and ultrafiltration failure. To determine whether glycation can occur in the environment of the dialysate, we have carried out studies using albumin as a model protein.
2. Glycated albumin was measured in the serum and dialysate of 46 patients on continuous ambulatory peritoneal dialysis (31 non-diabetic patients, 15 diabetic patients). Dialysate and serum glycated albumin (ranges 1.0-12.7% and 0.9-10.2%, respectively) were related to each other (r = 0.988, P &lt;0.001), but dialysate glycated albumin was significantly higher than serum glycated albumin (P &lt;0.0001), with the dialysate to serum glycated albumin ratio being greater than unity in 76% of patients (mean ratio 1.14). This implies either preferential transfer of glycated albumin across the peritoneal membrane or intraperitoneal glycation during the dwell period.
3. In vitro, significant glycation occurred in dialysate during a 6 h incubation period (P &lt;0.01) at a rate related to the glucose concentration in the dialysate (rs = 0.63, P &lt;0.05). The glycation rate was not significantly affected (P = 0.05) by factors other than the glucose concentration.
4. Our results demonstrate that protein glycation occurs within the peritoneum during continuous ambulatory peritoneal dialysis. Further studies are required to establish the relationship of glycation of structural proteins in the peritoneal membrane to membrane function.
Clenbuterol, a β-Adrenoceptor Agonist, Increases Relative Muscle Strength in Orthopaedic Patients
Authors: Maltin C. A. , Delday M. I. , Watson J. S. , Heys S. D. , Nevison I. M. , Ritchie I. K. , Gibson P. H. 
Published: August 2015

1. The sympathomimetic agent clenbuterol has a muscle-specific anabolic effect in normal and wasted muscles from animals. This trial was designed to examine the effect of the drug on the recovery of muscle strength and area after open medial meniscectomy.
2. A double-blind, completely randomized, placebo-controlled study was carried out on 20 healthy male patients. Muscle strength and cross-sectional area were determined before and after surgery. Patients were treated with drug or placebo for 4 weeks postoperatively and there was a 2 week washout period.
3. The results suggest that, in the operated leg, clenbuterol treatment is associated with a more rapid rehabilitation of strength in knee extensor muscles; in the unoperated leg, knee extensor strength increased above the initial values after 6 weeks (P = 0.01). However, in terms of absolute strength the differences were not significant between the two groups.
4. It is concluded that the data lend support to the proposition that clenbuterol has therapeutic potential in the treatment of muscle-wasting conditions.
Abnormal Urate Transport in Erythrocytes of Patients with Idiopathic Calcium Nephrolithiasis: A Possible Link with Hyperuricosuria
Authors: Gambaro Giovanni , Vincenti Massimo , Marchini Francesco , D'Angelo Angela , Baggio Bruno 
Published: August 2015

1. The demonstration of an inheritable anomaly of erythrocyte oxalate transport in ‘primary’ calcium nephrolithiasis suggested that this disease might be a generalized metabolic disorder characterized by a defect in cellular anion transport.
2. To determine whether this anomaly is restricted to oxalate alone, we studied erythrocyte transmembrane urate self-exchange in calcium-oxalate renal stone formers in whom urinary excretion of uric acid is frequently increased.
3. Abnormal urate self-exchange was found in 30% of the patients. The urate self-exchange rate constant was correlated with 24 h urinary excretion of uric acid; the erythrocyte anomaly was also associated with the frequency of hyperuricosuria and a more intense disease activity. Transmembrane urate self-exchange was inhibited by stilbene and heparan sulphate. Morphazinamide administration did not reduce urinary urate excretion in patients with abnormal urate erythrocyte self-exchange.
4. These findings suggest that hyperuricosuria during calcium-oxalate renal stone disease might be due to a cellular defect in urate transport, and further support the hypothesis that idiopathic nephrolithiasis is a metabolic disorder characterized by a defect in cellular anion transport.
Diffusion of Polyethylene Glycol-400 across Lipid Barriers in Vitro
Authors: Iqbal T. H. , Lewis K. O. , Cooper B. T. 
Published: August 2015

1. Polyethylene glycol has been used extensively as a probe to measure passive small-intestinal permeability in viro. However, there has been some uncertainty as to its suitability for use as an indicator of the permeation of water-soluble molecules across the intestinal wall because it seems to traverse the mucosa in much greater quantities than sugar molecules of equivalent Mr.
2. We have measured the permeation of polyethylene glycol-400 and lactulose from aqueous solution across pure lipid solvents in vitro. We found considerable transport of polyethylene glycol-400 across chloroform (1.03 g h−1 m−2) but no movement across petroleum ether.
3. However, in a separate experiment in which phospholipid (egg lecithin) was dissolved in the petroleum ether, permeation of polyethylene glycol-400 did occur (0.13 g h−1 m2), implying interaction of polyethylene glycol-400 with the phospholipid. No permeation of lactulose was seen in any of the experiments.
4. Our results suggest that, because of its interaction with lipid solvents, polyethylene glycol-400 is unsuitable as a probe to measure passive intestinal permeability in vivo.
Isolation of Human Cardiac Endothelin Receptors by a Peptide-Receptor Mobility Shift Assay
Authors: Persidis A. , Harcombe A. A. , Davenport A. P. , Kuc R. E. , Plumpton C. , Weissberg P. L. 
Published: August 2015

1. A peptide-protein mobility shift assay has been developed, using native polyacrylamide-gel electrophoresis, that enables the isolation of de-natured receptor proteins from small amounts of human cardiac tissue.
2. Radiolabeled endothelin-1 and related peptides were used to identify and isolate endothelin receptors from partially purified membrane extracts of human atrial tissue.
3. Binding analysis using radiolabelled endothelin-1 gave an equilibrium dissociation constant (Kd) of 2 nmol/l, similar to results from binding experiments conducted directly on tissue.
4. Peptide-receptor complexes were electroeluted from native gels and dissociated. Receptor material was characterized by dot-immunobinding analysis of eluates using an antibody raised against a predicted human endothelin receptor sequence.
Angiopeptin Inhibition of Myointimal Hyperplasia after Balloon Angioplasty of Large Arteries in Hypercholesterolaemic Rabbits
Authors: Howell Marcus H. , Adams Michael M. , Wolfe Mary S. , Foegh Marie L. , Ramwell Peter W. 
Published: August 2015

1. Currently, a wide range of drugs is being evaluated for the ability to prevent the restenosis which frequently accompanies percutaneous transluminal coronary angioplasty. Patients undergoing angioplasty are generally hypercholesterolaemic and therefore the possibility that plasma lipids may compromise the efficacy of anti-restenotic drugs must be assessed. A promising drug in several clinical trials for the prevention of restenosis is angiopeptin, an octapeptide analogue of somatostatin that possesses a highly lipophilic terminal.
2. The effect of angiopeptin on myointimal hyperplasia was studied in a rabbit model of arterial balloon catheter injury where the rabbits were made hypercholesterolaemic by a 0.5% cholesterol diet. The degree of subsequent myointimal thickening was measured by morphometry.
3. Angiopeptin (20 μg day−1 kg−1) significantly inhibited myointimal thickening by an average of 47% in the infrarenal aorta and both the common and external iliac arteries in the presence of elevated plasma lipids concentrations. Low dose angiopeptin (2 μg day−1 kg−1) significantly inhibited myointimal thickening in the external iliac artery but not in the other two vessels.
4. Angiopeptin treatment (20 μg day−1 kg−1) did not significantly modify the plasma cholesterol, very-low-density lipoprotein, intermediate-sized low-density lipoprotein, low-density lipoprotein and high-density lipoprotein concentrations that were elevated by the 0.5% cholesterol diet.
5. We conclude that the inhibitory effect of angiopeptin is largely unaffected by elevated plasma lipid concentrations and that this drug did not modify plasma lipid concentrations in rabbits.
Independent, Marked Associations of Alleles of the Insulin Receptor and Dipeptidyl Carboxypeptidase-1 Genes with Essential Hypertension
Authors: Morris Brian J. , Zee Robert Y. L. , Ying Li-Hua , Griffiths Lyn R. 
Published: August 2015

1. There is evidence to suggest that essential hypertension is a polygenic disorder and that it arises from yet-to-be-identified predisposing variants of certain genes that influence blood pressure. The cloning of various hormone, enzyme, adrenoceptor and hormone receptor genes whose products are involved in blood pressure control and the identification of polymorphisms of these has permitted us to test their genetic association with hypertension.
2. Cross-sectional analyses of a number of candidate gene markers were performed in hypertensive and normotensive subjects who were selected on the basis of both parents being either hypertensive or normotensive, respectively, and the difference in total alleles on all chromosomes for each polymorphism between the hypertensive and normotensive groups was tested by χ2 analysis with one degree of freedom.
3. A marked association was observed between hypertension and insertion alleles of polymorphisms of the insulin receptor gene (INSR) (P &lt;0.0040) and the dipeptidyl carboxypeptidase-1 (angiotensin I-converting enzyme; kininase II) gene (DCP1) (P &lt;0.0018). No association with hypertension was evident, however, for polymorphisms of the growth hormone, low-density lipoprotein receptor, renal kalli-krein, α2- and β1-adrenoreceptor, atrial natriuretic factor and insulin genes.
4. All but one of the hypertensive subjects had at least one of the hypertension-associated alleles, and although subjects homozygous for both were three times more frequent in the hypertensive group, examination of the nine possible genotypes suggested that the INSR and DCP1 alleles are independent markers for hypertension.
5. The present results suggest that genetic variant(s) in close linkage disequilibrium with polymorphisms at INSR and DCP1 may be involved in part in the aetiology of essential hypertension.
Glutathione Peroxidase Activity and Metabolism of Arachidonic Acid in Peripheral Blood Mononuclear Cells from Elderly Subjects
Authors: Meskini N. , Nemoz G. , Chapuy P. , Haond P. , Pageaux J. F. , Vericel E. , Lagarde M. , Prigent A. F. 
Published: August 2015

1. Since ageing has been associated with a decrease in both immune responses and antioxidant defences, this study was undertaken to compare the glutathione peroxidase activity in peripheral blood mononuclear cells of healthy elderly and young donors. The mean value of glutathione peroxidase activity was significantly lower in the aged group (−36%) than that observed in the young control group (n = 10).
2. This defect was accompanied by a marked increase (+106%) in the oxygenated metabolism of endogenous arachidonic acid by lipoxygenases as judged by the radiolabel associated with hydroxyeicosatetraenoic acids in [3H]arachidonic acid-prelabelled peripheral blood mononuclear cells, whereas the cyclo-oxygenase activity, estimated by the radiolabel associated with thromboxane B2, was not significantly altered.
3. Upon stimulation by the mitogenic lectin concanavalin A, the radioactivity associated with total eicosanoids (free arachidonic acid plus hydroxyeicosatetraenoic acids plus thromboxane B2) was significantly increased over basal levels in the peripheral blood mononuclear cells of both the elderly and the control groups. However, the mitogen-induced increase was lower in the elderly group (+48%) than in the control group (+131%). Upon concanavalin A stimulation, the radioactivity of hydroxyeicosatetraenoic acids was increased by only 96% in peripheral blood mononuclear cells from the elderly group compared with 350% in control cells. Similarly, the radioactivity associated with thromboxane B2 was increased by only 82% in peripheral blood mononuclear cells from the elderly group compared with 218% in control cells.
4. Reverse phase h.p.l.c. of the hydroxyeicosatetraenoic acids showed that, in unstimulated peripheral blood mononuclear cells, the 12-hydroxyeicosatetra-enoic acid level tended to be higher in the elderly group than in the control group, which might be indicative of an hyperactivity of the contaminating platelets in peripheral blood mononuclear cells from elderly subjects. However, in stimulated cells, the concanavalin A-induced increase in 12-hydroxyeico-satetraenoic acid proved to be lower in the elderly group (+ 283%) than in the control group (+ 814%). 5. Furthermore, the concanavalin A-induced release of arachidonic acid from the phosphoinositide pool was also decreased in the elderly group as compared with the control group. These results suggest that the major defect of arachidonic acid metabolism in peripheral blood mononuclear cells from elderly subjects might be located at the level of its mitogen-induced liberation known to occur during the early steps of lymphocyte activation. An eventual implication of the lowered glutathione peroxidase activity in the observed abnormalities of arachidonic acid metabolism in cells from aged subjects is discussed.
Comparison between Continuous and Discrete Measurements of Breathlessness during Exercise in Normal Subjects Using a Visual Analogue Scale
Authors: Harty Helen R. , Heywood Peter , Adams Lewis 
Published: August 2015

1. Visual analogue scaling of breathlessness made at discrete intervals during ventilatory stimulation tests can provide useful information about the intensity of this sensation. The aim of the present study was to investigate the use of continuous visual analogue scaling as a means of improving the temporal resolution of this measurement.
2. Six normal naive subjects scaled breathlessness using a visual analogue scale, during steady-state exercise. Further changes in this sensation were induced by either sustained hypercapnia or acute hypoxia; these responses were assessed either continuously or at discrete 30 s intervals and the two scaling methods were compared.
3. The continuous method of assessing breathlessness compared favourably with that of the more established discrete method, providing reproducible measurements in repeated tests equivalent in intensity to those obtained every 30 s.
4. Transient changes in the sensation of breathlessness produced by acute episodes of hypoxia were identified using the continuous scaling method but not with discrete scaling.
5. The continuous method of scaling breathlessness should aid the investigation of the neurophysiological basis of this sensation by allowing temporal relationships between changes in respiratory variables and the sensory consequences to be more carefully defined.