bluuebunny/crossref_metadata_2025_split huggingface dataset:
Haemodynamic and Biochemical Responses to l-Arginine and l-Lysine Infusions in Normal Subjects: l-Arginine-Induced Vasodilatation Cannot be Explained by Non-Specific Effects of Cationic Amino Acids
Authors: Smulders R. A. , Aarsen M. , Teerlink T. , De Vries P. M. J. M. , Van Kamp G. J. , Donker A. J. M. , Stehouwer C. D. A. 
Published: August 2015

1. Pharmacological stimulation of the synthesis of nitric oxide (NO) may be important in the prevention or treatment of cardiovascular diseases.
2. There is much discussion as to whether the precursor of NO, l-arginine, is able to stimulate basal endothelial NO production. l-Arginine is known to have vasodilating effects. However, it is not clear whether l-arginine-induced vasodilatation is attributable to an increase in NO production or to other systemic effects of l-arginine.
3. To investigate further the mechanisms of the l-arginine-induced vasodilatation, we compared the responses to l-arginine with those to saline and l-lysine in healthy subjects. l-Lysine is not a substrate for NO synthesis, but shares many of l-arginine's other properties.
4. During l-arginine infusion, blood pressure decreased [systolic blood pressure from 120.2 (SD 8.8) to 117.3 (12.1) mmHg (P = 0.05); diastolic blood pressure from 65.3 (5.9) to 61.6 (7.9) mmHg (P &lt; 0.01)], and heart rate and extracellular fluid volume increased. The total peripheral vascular resistance decreased during l-arginine infusion by 18.0 (11.4)% (P ≤ 0.05 compared with baseline and compared with l-lysine infusion). These results indicate vasodilatation. No changes were observed during l-lysine and saline infusion.
5. Plasma cyclic GMP (the second messenger for NO) increased during l-arginine but also during l-lysine infusion [from 5.7 (1.2) to 6.8 (1.7) nmol/l (P &lt; 0.01), and from 5.8 (1.8) to 7.0 (2.9) nmol/l (P &lt; 0.05) respectively]. Plasma l-citrulline (a by-product of NO synthesis from l-arginine) increased during l-arginine infusion from 30.6 (7.5) to 47.1 (9.9) μmol/l (P &lt; 0.001), but also during l-lysine infusion from 32.7 (6.5) to 42.0 (8.3) μmol/l (P &lt; 0.001).
6. Plasma electrolytes and atrial natriuretic peptide concentrations responded similarly to l-arginine and l-lysine infusion, indicating similar effects on osmolality, plasma volume expansion and potassium distribution.
7. In conclusion, although l-lysine infusion had effects that were similar to those of l-arginine infusion, no vasodilatation was observed. Therefore, these effects cannot account for the l-arginine-induced vasodilatation. This finding indirectly supports the hypothesis that the vasodilatation during l-arginine infusion might be mediated by an increase in NO synthesis. If so, our data suggest that the presumed markers for NO synthesis, plasma cyclic GMP and l-citrulline concentrations, do not accurately reflect this increase. Instead, the rise in plasma cyclic GMP may be related to the rise in ANP. The rise in l-citrulline may be related to competition with l-arginine for the same cell membrane transport mechanism and to stimulation of the urea cycle.
Resting Membrane Potential of Skeletal Muscle Calculated from Plasma and Muscle Electrolyte and Water Contents
Authors: Forsberg A. M. , Bergström J. , Lindholm B. , Hultman E. 
Published: August 2015

1. A method is described that enables the calculation of resting membrane potential from the electrolyte and water contents in blood plasma and in a sample of human muscle tissue obtained by the percutaneous needle-biopsy technique. In this calculation, the previously described equations for calculating resting membrane potential via the intra- and extra-cellular distribution of chloride were combined with the equation utilizing potassium distribution over the cell membrane.
2. The method of calculation was applied to 60 healthy subjects divided into three groups aged 19–40, 41–60 and 61–85 years. The calculated resting membrane potential in the subjects as a whole was −88.4 mV (SD 1.35; n = 60). A lower value was observed in the group aged 61–85 years (−87.7 mV, SD 1.0; n = 12) than in the group aged 19–40 years (−88.6 mV; SD 1.4; n = 32). No difference was observed between female and male subjects.
3. The RMP calculated with the present method in 60 healthy subjects was also compared with previously published values in healthy subjects, measured by the Clarke electrode method, and with values calculated from electrolyte and water distribution measured by isotope-dilution techniques. The results obtained in healthy subjects with different techniques were very similar. Data were analysed from earlier published studies in experimental animals in which resting membrane potential ranged from −91 to −65 mV. The resting membrane potential calculated from electrolytes in plasma and muscle showed a very good agreement with resting membrane potential recorded directly.
Comparison of the Effects on Urinary Sodium Excretion of Indomethacin and of Carbidopa in normal Volunteers given an Intravenous Saline Infusion
Authors: Stokes G. S. , Monaghan J. C. , Pillai D. N. 
Published: August 2015

1. Dopamine and prostaglandins are putative endogenous natriuretic hormones. The role of each in facilitating natriuresis induced by intravenous saline infusion was examined in normal volunteers in relation to administration of carbidopa, a dopadecarboxylase inhibitor, and indomethacin, an inhibitor of prostaglandin synthetase.
2. In a placebo-controlled, randomized study, 13 subjects received carbidopa (100 mg) and 12 received indomethacin (50 mg). Proximal and distal renal tubular Na+ reabsorption were determined using exogenous lithium clearance.
3. On the control day, 2 litres of 0.9% saline (308 mmol Na+) given intravenously in 3 h, resulted in volume expansion and natriuresis. Carbidopa reduced the urinary dopamine/noradrenaline ratio but showed no anti-natriuretic effect and no effect on fractional Na+ reabsorption. Indomethacin diminished natriuresis and increased distal fractional Na+ reabsorption in proportion to the anti-natriuretic effect.
4. The changes in plasma concentrations of albumin, aldosterone, atrial natriuretic peptide and renin activity associated with volume expansion were not modified by either carbidopa or indomethacin. Urinary prostaglandin E2 excretion was decreased transiently by indomethacin and was unaffected by carbidopa.
5. This study suggests that prostaglandins may modulate urinary Na+ excretion during saline-induced natriuresis through inhibition of distal tubular Na+ reabsorption. No role for free dopamine as a modulator of renal Na+ handling could be assigned on the basis of the findings with carbidopa.
The Effects of Low-Density Lipoprotein and High-Density Lipoprotein on Blood Viscosity Correlate with their Association with Risk of Atherosclerosis in Humans
Authors: Sloop Gregory D. , Garber David W. 
Published: August 2015

1. Increased blood or plasma viscosity has been observed in almost all conditions associated with accelerated atherosclerosis. Cognizant of the enlarging body of evidence implicating increased viscosity in atherogenesis, we hypothesize that the effects of low-density lipoprotein and high-density lipoprotein on blood viscosity correlate with their association with risk of atherosclerosis.
2. Blood viscometry was performed on samples from 28 healthy, non-fasting adult volunteers using a capillary viscometer. Data were correlated with haematocrit, fibrinogen, serum viscosity, total cholesterol, high-density lipoprotein-cholesterol, triglycerides and calculated low-density lipoprotein-cholesterol.
3. Low-density lipoprotein-cholesterol was more strongly correlated with blood viscosity than was total cholesterol (r = 0.4149, P = 0.0281, compared with r = 0.2790, P = 0.1505). High-density lipoprotein-cholesterol levels were inversely associated with blood viscosity (r = −0.4018, P = 0.0341).
4. To confirm these effects, viscometry was performed on erythrocytes, suspended in saline, which had been incubated in plasma of various low-density lipoprotein/high-density lipoprotein ratios. Viscosity correlated directly with low-density lipoprotein/high-density lipoprotein ratio (n = 23, r = 0.8561, P &lt; 0.01).
5. Low-density lipoprotein receptor occupancy data suggests that these effects on viscosity are mediated by erythrocyte aggregation.
6. These results demonstrate that the effects of low-density lipoprotein and high-density lipoprotein on blood viscosity in healthy subjects correlate with their association with risk of atherosclerosis. These effects on viscosity may play a role in atherogenesis by modulating the dwell or residence time of atherogenic particles in the vicinity of the endothelium.
Effects of Hydroxyurea Administration on the Body Weight, Body Composition and Exercise Performance of Patients with Sickle-Cell Anaemia
Authors: Hackney A. C. , Hezier W. , Gulledge T. P. , Jones S. , Strayhorn D. , Busby M. , Hoffman E. , Orringer E. P. 
Published: August 2015

1. As an ancillary study carried out during the recently completed Multicenter Study of Hydroxyurea, we examined the effect of hydroxyurea on the body weight, body composition and exercise capacity of adult patients with sickle-cell anaemia.
2. The subjects received either hydroxyurea (six males and four females) or placebo (eight males and six females). Data for each subject were generated during four separate 24 h admissions to the General Clinical Research Center. These admissions occurred at baseline and then at 6, 12 and 18 months after the start of study drug (hydroxyurea or placebo) administration. During each admission, body composition was measured by using a dual X-ray absorptiometer, and exercise testing was performed by cycle ergometry. Anaerobic performance was assessed according to a ‘Wingate’ protocol (20 s at maximal intensity against a cycling resistance of 7.5% body weight). Aerobic performance was examined using a steady state submaximal exercise protocol (10 min cycling time).
3. At baseline, no significant difference in any parameter was found between the hydroxyurea- and placebo-treated groups. At 18 months, the hydroxy-urea-treated subjects exhibited an average weight gain of 3.16 kg. The mean weight gain in the placebo-treated subjects was 1.82 kg. Body composition analysis showed that the additional weight in both groups involved both lean and fat body mass components. In anaerobic performance, the subjects given hydroxyurea showed an increase in peak muscle power of 104.9 W. The placebo group also showed an increase, but theirs was a more modest gain of 57.7 W. The most marked improvement in anaerobic performance was observed in the hydroxyurea-treated men (P &lt; 0.05). In aerobic performance, the hydroxyurea-treated subjects exhibited a decrease in peak heart rate response to a standardized workload of 15.2 beats/min, as compared with a decrease of only 4.3 beats/min in the placebo-treated patients.
4. Taken together, the overall weight gain, combined with increases in both anaerobic muscular performance and aerobic cardiovascular efficiency, provides objective data to support the subjective impression that hydroxyurea administration produces an improvement in the physical capacity of patients with sickle-cell anaemia.
Renal Endothelin System in Obstructive Jaundice: Its Role in Impaired Renal Function of Bile-Duct Ligated Rats
Authors: Kramer Herbert J. , Schwarting Kriemhild , Backer Angela , Meyer-Lehnert Harald 
Published: August 2015

1. Obstructive jaundice predisposes the kidney to acute renal failure. Endothelin (ET), a potent renal vasoconstrictor and modulator of the tubular action of arginine vasopressin, has been suggested to play a pathogenetic role in acute renal failure. In the present study we therefore investigated renal function and the renal ET system in rats on day 4 after bile-duct ligation (BDL) or sham-operation (SO), without (n = 7 in each group) and with treatment with bosentan, a combined ETA/ETB receptor blocker, (n = 5 in each group).
2. On day 4 after BDL, serum bilirubin had increased to 226 ± 10 μmol/l (SEM) as compared with 6 ± 2 μmol/l in SO rats. Endogenous creatinine clearance, an index of glomerular filtration rate, was significantly reduced to 0.7 ± 0.1 ml min−1 g−1 of kidney weight after BDL as compared with 1.1 ± 0.1 ml min−1 g−1 of kidney weight after SO (P &lt; 0.05). Bosentan prevented the decrease in glomerular filtration rate (1.0 ± 0.2 ml min−1 g−1 of kidney weight), as well as polyuria and defective concentrating ability, in BDL rats.
3. Plasma ET concentration on day 4 after surgery (28.2 ± 1.5 pmol/l) was higher (P &lt; 0.01) in BDL than in SO rats (12.9 ± 1.5 pmol/l) and rose further in bosentan-treated BDL and SO rats (43.4 ± 5.1 compared with 21.9 ± 6.6 pmol/l). Urinary ET excretion was significantly higher in BDL rats than in SO rats (1.58 ± 0.22 compared with 1.28 ± 0.18 pmol 24h−1 100 g−1 of body weight; P &lt; 0.05).
4. ET synthesis by glomeruli isolated from BDL rats was lower [81 ± 19 fmol h−1 (mg of protein)−1] than that from SO-rats [139 ± 28 fmol h−1 mg of protein)−1; P &lt; 0.05], whereas papillary ET synthesis was higher in BDL [10 ± 3 fmol h−1 (mg of protein)−1] than in SO rats [4 ± 1 fmol h−1 (mg of protein)−1; P &lt; 0.05].
5. The results indicate that BDL is associated with increased plasma ET concentration and suppression of GFR. Enhanced renal inner medullary collecting-duct ET synthesis, which is reflected by increased urinary ET excretion, may reduce distal tubular water absorption in BDL rats. Increased circulating and renal papillary ET synthesis may thus contribute to renal dysfunction and predispose the kidney to acute renal failure in obstructive jaundice.
13C-Urea Breath Test for Helicobacter Pylori: Cut-off Point Determination by Cluster Analysis
Authors: Mion Françcois , Rosner Gaëlle , Rousseau Marina , Minaire Yves 
Published: August 2015

1. This study was performed on a large set of 13C-urea breath test results to determine the optimal cut-off point of the test for the diagnosis of Helicobacter pylori (Hp) infection.
2. The following steps were applied to three sets of urea breath test results obtained in three groups of subjects (696 adults before anti-Hp treatment, 1056 adults after anti-Hp treatment and 173 children under 17 years of age): (1) demonstrate the distribution of urea breath test results as a mix of two normal populations (Hp negative and Hp positive) by logarithmic transformation of the results in each group of subjects; (2) apply statistical cluster analysis to determine the separation point between Hp-negative and -positive populations; (3) calculate the mean and SD of each population, and use these parameters in the equation of the normal distribution to establish the frequency curves of Hp-negative and -positive populations; and (4) determine the cut-off point of the urea breath test as the intersection of the two curves, and the risks of error related to it.
3. The optimal cut-off point was found at +3.00 δ%0/00, with a risk of false-negative or -positive response of the urea breath test of less than 3%. From this, a cut-off point of +3.00 δ%0/00 for the 13C-urea breath test is recommended, with an indetermined zone between +2.5 and +3.5 δ0/00 to account for the spontaneous variation of 13CO2 in breath and the limits of GC—isotope ratio-MS analytical precision.
Transport of l-Arginine and the Nitric Oxide Inhibitor NG-Monomethyl-l-Arginine in Human Erythrocytes in Chronic Renal Failure
Authors: Ribeiro A. C. Mendes , Hanssen H. , Kiessling K. , Roberts N. B. , Mann G. E. , Ellory J. C. 
Published: August 2015

1. Transport of l-arginine and the nitric oxide synthase inhibitors NG-monomethyl-l-arginine and NG-nitro-l-arginine was investigated in human erythrocytes from healthy donors and uraemic patients on haemodialysis.
2. Although Km values for total l-arginine influx were not significantly different in erythrocytes freshly isolated from controls or uraemic patients, uraemia was associated with an increase in the Vmax for transport (826 compared with 1176 μmol h−1 l−1 of cells) which was reduced to control values after dialysis.
3. Saturable influx of l-arginine was mediated by the classical cationic amino acid transport system y+ and system y+L, known to transport cationic and neutral amino acids with higher affinity.
4. Under zero-trans conditions, the Vmax for l-arginine transport via system y+ increased from 271 to 700 μmol h−1 l−1 of cells in uraemia, while Km values increased from 44 to 94 μmol/l. Dialysis had no significant effect on the kinetic parameters altered by uraemia.
5. Under zero-trans conditions, and with system y+ inhibited by N-ethylmaleimide (0.2 mmol/l), transport of l-arginine via system y+L was unaffected by uraemia.
6. Saturable influx of NG-monomethyl-l-arginine was also mediated by systems y+ (Km = 56 μmol/l, Vmax = 353 μmol h−1 l−1 of cells) and y+L (Km = 17 μmol/l, Vmax = 51.3 μmol h−1 l−1 of cells) and, as with l-arginine, uraemia increased the transport capacity for NG-monomethyl-l-arginine.
7. Influx of the neutral nitric oxide synthase inhibitor NG-nitro-l-arginine was not readily saturable.
8. Intracellular concentrations of l-arginine and NG-monomethyl-l-arginine were significantly increased in erythrocytes from uraemic patients when compared with controls, consistent with an increased transport capacity for l-arginine and NG-monomethyl-l-arginine.
9. The present study provides evidence that system y+ mediates the increased transport of l-arginine and NG-monomethyl-l-arginine in human erythrocytes from patients with chronic renal failure. Our findings may have implications for the activity of the l-arginine—nitric oxide signalling pathway in vascular endothelial and smooth-muscle cells in uraemia.
Effects of Physical Training on Metabolic Control in Elderly Type 2 Diabetes Mellitus Patients
Authors: Ligtenberg P.C. , Hoekstra J.B.L. , Bol E. , Zonderland M.L. , Erkelens D.W. 
Published: August 2015

1. The specific role of physical activity in the treatment of type 2 diabetes is still subject to discussion. A randomized prospective study was performed, investigating both the influence of physical training on metabolic control and the feasibility of physical training in the elderly.
2. A total of 58 patients (mean age: 62 ± 5 years; range: 55–75 years) with type 2 diabetes were randomized to either a physical training or a control programme. The training programme consisted of three sessions a week, aiming at 60–80% of the maximal oxygen uptake (VO2max). The 12 week supervised period was followed by a 14 week non-supervised one. The control group followed an educational programme. VO2max was assessed during exercise on a cycle ergometer. Glycosylated haemoglobin (HbA1c) was used as a measure for glucose control, and an insulin tolerance test was performed to test insulin sensitivity. Multivariate analysis of variance, with repeated measures design, was used to test differences between groups.
3. Fifty-one patients completed the study. VO2max was higher in the training group than in the control group both after 6 weeks (P ≤ 0.01 between groups) and after 26 weeks [training group: 1796 ± 419 ml/min (prestudy), 1880 ± 458 ml/min (6 weeks), 1786 ± 591 ml/min (26 weeks); control group: 1859 ± 455 ml/min (prestudy), 1742 ± 467 ml/min (6 weeks), 1629 ± 504 ml/min (26 weeks)]. Blood glucose control and insulin sensitivity did not change during the study. Levels of total triacyl-glycerols, very-low-density lipoprotein-triacyl-glycerols and apolipoprotein B were significantly lower after 6 weeks (P ≤ 0.01, P ≤ 0.05, P ≤ 0.05 between groups respectively), and so was the level of total cholesterol after 12 weeks of training (P ≤ 0.05 between groups).
4. Physical training in obese type 2 diabetic patients over 55 years of age does not change glycaemic control or insulin sensitivity in the short-term. Regular physical activity may lower triacylglycerol and cholesterol levels in this group of patients.
5. Finally, physical training in motivated elderly type 2 diabetic patients without major cardiovascular or musculoskeletal disorders is feasible, but only under supervision.
Early Protein Restriction and Obesity Independently Induce Hypertension in 1-Year-Old Rats
Authors: Petry Clive. J. , Ozanne Susan E. , Wang Chun Li , Hales C. Nicholas 
Published: August 2015

1. Recent studies have revealed a link between fetal and early post-natal growth retardation and the development of features of the insulin resistance syndrome in later life. Obesity is also a strong risk factor for this syndrome. The aim of this study was to assess whether maternal and early protein restriction, which causes growth retardation, and obesity are risk factors that are independent for the development of certain features of the insulin resistance syndrome, especially hypertension.
2. Pregnant Sprague—Dawley rats were given either 20% or 8% protein isocaloric diets throughout pregnancy and lactation. Female offspring were weaned onto the same diets as their mothers and they remained on these diets until 70 days of age. Half the rats were then given standard laboratory chow, whilst the remainder were fed a highly palatable cafeteria-style diet. Rats were maintained on these diets for the remainder of the study.
3. Rats given the 8% protein diet remained physically lighter than comparable animals fed the 20% protein diet throughout the study. In contrast, cafeteria-fed rats showed excessive weight gain. At 1 year of age the rats had their systolic blood pressures and fasting lipids measured, as well as undergoing an intraperitoneal glucose-tolerance test.
4. Cafeteria-fed rats had worse glucose tolerances than controls and hypertriacylglycerolaemia. The early 8% protein rats had significantly increased blood pressures, as did the cafeteria-fed rats. These increases were additive, suggesting that early protein restriction, and later obesity, are indeed independent risk factors for the development of hypertension.
Impaired Insulin-Induced Attenuation of Noradrenaline-Mediated Vasoconstriction in Insulin-Resistant Obese Zucker Rats
Authors: Walker A. B. , Dores J. , Buckingham R. E. , Savage M. W. , Williams G. 
Published: August 2015

1. Insulin resistance is associated with hypertension but the underlying mechanism is unclear. We tested the hypothesis that insulin-induced vasodilatation is impaired in insulin-resistant obese Zucker rats. We studied mesenteric artery (≈ 220 μm diameter) function before the development of hypertension in 3-month old obese Zucker rats and age-matched lean rats.
2. In vessels from lean rats, insulin at concentrations of 50, 500 and 5000 m-units/l attenuated the constriction in response to noradrenaline (50 m-units/l: 8 ± 3%, P &lt; 0.05; 500 m-units/l: 13 ± 3%, P &lt; 0.02; 5000 m-units/l: 13 ± 2%, P &lt; 0.02).
3. Vessels from obese rats failed to show any such response to insulin (2 ± 6% increase in maximal tension with 5000 m-units/l; not significant), both in the presence and absence of l-arginine (3 mmol/l).
4. Vessels from obese rats showed slight but significant impairment in the vasodilator response to acetylcholine (5 × 10−8−10−4 mol/l) (obese: 64.1 ± 3.7% relaxation; lean: 77.3 ± 3.7% relaxation; P &lt; 0.05); however, relaxation in response to A23187 was not significantly different between the phenotypes (obese: 81.3 ± 10.6% relaxation; lean: 79.1 ± 9.7% relaxation; not significant).
5. Systolic blood pressure was not significantly different in lean (126 ± 8 mmHg) and obese (127 ± 7 mmHg) rats at the time of study (not significant).
6. We conclude that insulin-induced attenuation of noradrenaline-mediated vasoconstriction is impaired in the obese Zucker rat and that this defect precedes and therefore could contribute to the development of hypertension in this insulin-resistant model. The defect in insulin action could reside in the endothelial generation of nitric oxide, as endothelial function is also abnormal.