bluuebunny/crossref_metadata_2025_split huggingface dataset:
Absence of glutamine isotopic steady state: implications for the assessment of whole-body glutamine production rate
Authors: ACKER Bernadette A. C. VAN , HULSEWÉ Karel W. E. , WAGENMAKERS Anton J. M. , DEUTZ Nicolaas E. P. , KREEL Bernard K. VAN , HALLIDAY Dave , MATTHEWS Dwight E. , SOETERS Peter B. , MEYENFELDT Maarten F. VON 
Published: August 2015

1.During infusion of [5-15N]glutamine in patients with gastrointestinal cancer we unexpectedly observed a gradual decrease in time of the appearance rate (Ra) of glutamine in plasma. Here we investigate whether the failure to achieve a plateau isotopic enrichment in plasma is, among other factors, due to incomplete equilibration of the glutamine tracer with the large intramuscular free glutamine pool.
2.Plasma and intramuscular glutamine enrichment were measured during 6–11 ;h infusions of L-[5-15N]glutamine and L-[1-13C]glutamine in post-absorptive patients admitted to hospital for elective abdominal surgery. L-[1-13C]Leucine and L-[ring-2H5]phenylalanine were infused to measure the proportion of glutamine appearing in plasma directly due to its release from protein.
3.The glutamine tracer entered muscle, but the rise in intramuscular glutamine enrichment was small, presumably as a result of the enormous size of the intramuscular glutamine pool and the limited speed of entry of glutamine into muscle. In each patient the intramuscular glutamine enrichment was lower than that in plasma (P &lt; 0.001), and both increased with tracer infusion time (P &lt; 0.001), indicating incomplete equilibration of the glutamine tracer.
4.A comparison of the results obtained by the two glutamine tracers indicated that recycling of the nitrogen label contributed to about 15% of the decrease in Ra.
5.There was a gradual reduction in the glutamine release from proteolysis, which contributed to 16–21% of the decline in Ra.
6.We conclude that slow equilibration of the glutamine tracer with the large muscle glutamine pool significantly contributes to the absence of isotopic steady state. Consequently, the appearance rate of glutamine in plasma measured during short tracer infusion periods (hours) considerably overestimates the whole-body glutamine flux.
Effect of interleukin-4 on pro-inflammatory cytokine production and the acute phase response in healthy individuals and in patients with cancer or multiple organ failure
Authors: WIGMORE Stephen J. , MAINGAY Jean P. , FEARON Kenneth C. H. , O'RIORDAIN Michael G. , ROSS James A. 
Published: August 2015

1.This study investigates whether previously documented effects of interleukin-4 in down-regulating pro-inflammatory cytokine production by peripheral blood mononuclear cells (PBMCs) from healthy individuals would be reproducible in PBMCs isolated from patients with multiple organ failure (acute disease model) and gastrointestinal cancer (chronic disease model). The effects of interleukin-4 on the ability of PBMC supernatants to elicit an acute phase protein response from isolated human hepatocytes were also studied.
2.Incubation of PBMCs with interleukin-4 significantly reduced both spontaneous and lipopolysaccharide-induced production of tumour necrosis factor and lipopolysaccharide-induced interleukin-6 production, demonstrating that the PBMCs from patients with acute and chronic disease are not refractory to the effects of interleukin-4. The effects of interleukin-4 on the ability of PBMCs from the groups studied to elicit an acute phase response were complex and varied both between patient groups and individual acute phase proteins. Overall, interleukin-4 reduced the potential of PBMCs to stimulate production of the positive acute phase proteins C-reactive protein, α1-antichymotrypsin and α1-acid glycoprotein.
3.This work emphasizes the pleiotropic nature of cytokines and the complex regulatory mechanisms which exist. The study illustrates the difficulties in devising in vivo intervention strategies using cytokines such as interleukin-4.
Importance of glutamine metabolism in murine macrophages and human monocytes to L-arginine biosynthesis and rates of nitrite or urea production
Authors: MURPHY Colin , NEWSHOLME Philip 
Published: August 2015

1.The intermediates of biochemical cycles are commonly utilized for biosynthetic processes; thus at least one intermediate must be replenished de novo to provide constant flux through the cycle. The utilization of l-arginine for NO synthesis in macrophages may thus reduce the concentration of intermediates of the urea cycle. It is possible that a glutamine-utilizing pathway exists in mononuclear phagocytes that may connect with the urea cycle.
2.In this paper we report that mouse peritoneal resident and Bacillus Calmette–Guerin (BCG)-activated macrophages and human monocytes are capable of utilizing glutamine at high rates, contain sufficient activity of the enzymes required to convert glutamine to citrulline (and subsequently citrulline to arginine) to account for observed rates of nitrite synthesis in the absence of extracellular l-arginine, and will release nitrite when exposed to intermediates of the proposed glutamine → arginine pathway.
3.The rate of nitrite production (in the absence of extracellular arginine) was reduced by culturing macrophages or monocytes in the presence of the glutaminase inhibitor 6-diazo 5-oxo norleucine.
4.The rate and extent of arginase secretion, glutamine utilization, nitrite production (basal and lipopolysaccharide-stimulated) and phosphate-dependent glutaminase activity from BCG-activated macrophages was increased compared with resident cells.
5.We suggest that the elevated arginase secretion rates in activated macrophages would effectively increase the intracellular concentration of arginine available for conversion to NO via inducible nitric oxide synthase, the expression of which is known to increase on activation of macrophages or monocytes. Additionally, the rate of l-arginine biosynthesis from glutamine may be increased on immunostimulation of the macrophage.
Identification of oxidized low-density lipoprotein in human serum by NMR spectroscopy
Authors: JANKOWSKI J. , NOFER J.-R. , TEPEL M. , GRIEWEL B. , SCHLÜTER H. , ASSMANN G. , ZIDEK W. 
Published: August 2015

1.In this study we compared the 500 MHz 1H-NMRs from native and oxidized low-density lipoproteins.
2.The measurements revealed a characteristic pattern of three resonances in spectra from oxidized, but not from native low-density liprotein at 1.17 p.p.m., 1.18 p.p.m. and 1.20 p.p.m. (relative to 3-trimethylsilyl-[2,2,3,3-2H4]-propionate).
3.A quantitative comparison between these resonances in sera from patients with coronary heart disease and healthy control subjects revealed that the intensity was significantly higher in patients with coronary heart disease (1.17 p.p.m.: 0.026±0.014 versus 0.015±0.019; 1.18 p.p.m.: 0.032±0.011 versus 0.017±0.021; 1.20 p.p.m.: 0.030±0.066 versus 0.010±0.005; P< 0.05 compared with healthy control subjects for each resonance).
4.Fractionation of sera from patients with coronary heart disease revealed that the resonances equal to those obtained from experimentally oxidized low-density lipoprotein are indeed caused by the low-density lipoprotein fraction of the sera.
5.When the NMRs from sera were calibrated with oxidized low-density lipoprotein prepared by Cu2+ oxidation, a concentration of 66.5±28.6 ;μg/ml and 36.3±23.7 ;μg/ml (P< 0.05) was estimated in patients with coronary heart disease and healthy subjects respectively. Elevated levels of oxidized low-density lipoprotein also occurred in those patients with normal serum concentrations of total low-density lipoprotein.
6.The study shows a simple method to measure oxidized low-density lipoprotein in human serum and may gain interest to assess the cardiovascular risk factor profiles more completely.
Evaluation of potential factors affecting the measurement of cerebrovascular reactivity by near-infrared spectroscopy
Authors: TOTARO Rocco , BARATTELLI Giovanna , QUARESIMA Valentina , CAROLEI Antonio , FERRARI Marco 
Published: August 2015

1.Near-infrared (IR) spectroscopy is based on the relative transparency of skin, skull and brain to the light in the near-IR region (700–1100 ;nm) and on the oxygen-dependent tissue absorption changes of haemoglobin.
2.We evaluated the most relevant factors (reproducibility, venous return, age and sex) that might affect reliability of near-IR spectroscopy to test CO2 cerebrovascular reactivity.
3.Thirty-four healthy volunteers were enrolled in the study. The protocol consisted of a 3-min baseline, a 3-min hypercapnia (5% CO2 in air) and a 2-min recovery. Transcranial Doppler sonography measurements were simultaneously performed. The CO2 reactivity test was repeated on 27 subjects after 1 ;h to assess reproducibility. CO2 reactivity was also evaluated at different body positions (supine, 35° Trendelenburg and 35° reverse Trendelenburg), and over a gradual increase of the inspired CO2.
4.Changes in near-IR spectroscopy and transcranial Doppler sonography parameters were significantly correlated with variations of end-tidal CO2 (P< 0.005). A significant correlation between the reactivity indexes of near-IR spectroscopy parameters and flow velocity was also found (P< 0.01). A high reproducibility was also found for deoxyhaemoglobin (rI = 0.76), oxyhaemoglobin (rI = 0.68) and flow velocity (rI = 0.60) reactivity indexes. No significant differences between the reactivity indexes of different body positions were found (P> 0.05). The reactivity index of oxyhaemoglobin and deoxyhaemoglobin decreased (P< 0.05) and increased (P< 0.01) with age respectively.
5.We found that near-IR spectroscopy is a reliable and reproducible method for the evaluation of cerebrovascular reactivity and might be considered, after appropriate validation, for the assessment of patients with cerebrovascular disease.
Inhaled corticosteroid therapy reduces the early morning peak in cortisol and aldosterone
Authors: WILSON Andrew M. , SIMS Erika J. , STRUTHERS Allan D. , LIPWORTH Brian J. 
Published: August 2015

1.As mineralocorticoid and adrenocorticoid activity are both under the diurnal control of adrenocorticotropic hormone secretion, we aimed to evaluate whether the normal circadian rhythm of cortisol and aldosterone secretion was suppressed by inhaled corticosteroid therapy.
2.Ten normotensive patients with mild–moderate asthma, mean age 24.0 (S.D. 9.8) years and mean arterial pressure 90.7 (9.8) mmHg, were studied in a double-blind, randomized crossover design comparing placebo with fluticasone propionate, 1000 ;μg administered twice daily at 08:00 ;h and 20:00 ;h. After 5 days of repeated dosing at steady state, measurements were made of plasma cortisol and aldosterone at midnight and 08:00 ;h.
3.With placebo there was a significant (P< 0.05) difference between cortisol values at 08:00 ;h (588.6±83.8 ;nmol/l) and midnight (109.6±35.0 ;nmol/l), whereas after treatment with fluticasone propionate there was no significant difference between levels at 08:00 ;h (143.3±57.4 ;nmol/l) and midnight (64.3±22.3 ;nmol/l). For cortisol at 08:00 ;h there was also a significant (P< 0.05) difference between placebo and fluticasone propionate. The same pattern was observed for aldosterone. Plasma aldosterone levels at 08:00 ;h after treatment with placebo (129.6±30.9 ;nmol/l) were significantly different (P< 0.05) to those seen at midnight (40.4±6.2 ;nmol/l). After treatment with fluticasone propionate, there was no significant difference between levels at midnight (55.4±11.7 ;nmol/l) and 08:00 ;h (64.8±12.7 ;nmol/l).
4.These results show that inhaled corticosteroid therapy abolishes the circadian rhythm of aldosterone and cortisol secretion. This may have possible implications for patients taking inhaled corticosteroids in terms of the beneficial cardiac effects of suppressing early morning aldosterone.
Heart rate and flow velocity variability as determined from umbilical Doppler velocimetry at 10–20 weeks of gestation
Authors: URSEM Nicolette T. C. , STRUIJK Piet C. , HOP Wim C. J. , CLARK Edward B. , KELLER Bradley B. , WLADIMIROFF Juriy W. 
Published: August 2015

1.The aim of this study was to define from umbilical artery flow velocity waveforms absolute peak systolic and time-averaged velocity, fetal heart rate, fetal heart rate variability and flow velocity variability, and the relation between fetal heart rate and velocity variables in early pregnancy.
2.A total of 108 women presenting with a normal pregnancy from 10 to 20 weeks of gestation consented to participate in a cross-sectional study design. Doppler ultrasound recordings were made from the free-floating loop of the umbilical cord.
3.Umbilical artery peak systolic and time-averaged velocity increased at 10–20 weeks, whereas fetal heart rate decreased at 10–15 weeks of gestation and plateaued thereafter. Umbilical artery peak systolic velocity variability and fetal heart rate variability increased at 10–20 and 15–20 weeks respectively.
4.The inverse relationship between umbilical artery flow velocity and fetal heart rate at 10–15 weeks of gestation suggests that the Frank–Starling mechanism regulates cardiovascular control as early as the late first and early second trimesters of pregnancy. A different underlying mechanism is suggested for the observed variability profiles in heart rate and umbilical artery peak systolic velocity. It is speculated that heart rate variability is mediated by maturation of the parasympathetic nervous system, whereas peak systolic velocity variability reflects the activation of a haemodynamic feedback mechanism.
Cardiovascular autonomic modulation and activity of carotid baroreceptors at altitude
Authors: BERNARDI Luciano , PASSINO Claudio , SPADACINI Giammario , CALCIATI Alessandro , ROBERGS Robert , GREENE Richard , MARTIGNONI Emilia , ANAND Inder , APPENZELLER Otto 
Published: August 2015

1.To assess the effects of acute exposure to high altitude on baroreceptor function in man we evaluated the effects of baroreceptor activation on R–R interval and blood pressure control at high altitude. We measured the low-frequency (LF) and high-frequency (HF) components in R–R, non-invasive blood pressure and skin blood flow, and the effect of baroreceptor modulation by 0.1-Hz sinusoidal neck suction. Ten healthy sea-level natives and three high-altitude native, long-term sea-level residents were evaluated at sea level, upon arrival at 4970 ;m and 1 week later.
2.Compared with sea level, acute high altitude decreased R–R and increased blood pressure in all subjects [sea-level natives: R–R from 1002±45 to 775±57 ;ms, systolic blood pressure from 130±3 to 150±8 ;mmHg; high-altitude natives: R–R from 809±116 to 749±47 ;ms, systolic blood pressure from 110±12 to 125±11 ;mmHg (P&lt; 0.05 for all)]. One week later systolic blood pressure was similar to values at sea level in all subjects, whereas R–R remained elevated in sea-level natives. The low-frequency power in R–R and systolic blood pressure increased in sea-level natives [R–R-LF from 47±8 to 65±10% (P&lt; 0.05), systolic blood pressure-LF from 1.7±0.3 to 2.6±0.4 ln-mmHg2 (P&lt; 0.05)], but not in high-altitude natives (R–R-LF from 32±13 to 38±19%, systolic blood pressure-LF from 1.9±0.5 to 1.7±0.8 ln-mmHg2). The R–R-HF decreased in sea-level natives but not in high-altitude natives, and no changes occurred in systolic blood pressure-HF. These changes remained evident 1 week later. Skin blood flow variability and its spectral components decreased markedly at high altitude in sea-level natives but showed no changes in high-altitude natives. Neck suction significantly increased the R–R- and systolic blood pressure-LF in all subjects at both sea level and high altitude.
3.High altitude induces sympathetic activation in sea-level natives which is partially counteracted by active baroreflex. Despite long-term acclimatization at sea level, high-altitude natives also maintain active baroreflex at high altitude but with lower sympathetic activation, indicating a persisting high-altitude adaptation which may be genetic or due to baroreflex activity not completely lost by at least 1 year's sea-level residence.
Augmented effects of methionine and cholesterol in decreasing the elastic lamina while thickening the aortic wall in the rat aorta
Authors: ZULLI Anthony , BUXTON Brian F. , DOOLAN Laurie , LIU James J. 
Published: August 2015

1.Patients with an elevated plasma level of either homocysteine or cholesterol are at increased risk of cardiovascular disease. Both methionine, the precursor of homocysteine, and cholesterol are found primarily in the same foods; therefore we investigated the effect of methionine feeding alone, cholesterol feeding alone, and both, on the thickness of the aortic wall and the aortic elastic lamina of normotensive animals.
2.Twenty normotensive rats were divided into four groups of five animals. The following diet was administered for 15 weeks: normal chow; normal chow supplemented with 2% methionine; normal chow supplemented with 2% cholesterol; normal chow supplemented with 2% methionine+2% cholesterol.
3.The results showed a 3-fold decrease (P&lt; 0.003) in the aortic elastic lamina in the 2% methionine group and a 2.5-fold decrease in the 2% cholesterol group compared with the normal chow group. There was a 9-fold (P&lt; 0.0003) decrease in the 2% methionine+2% cholesterol group compared with the normal chow group. Furthermore, feeding with methionine plus cholesterol significantly increased aortic wall thickness compared with the methionine group, cholesterol group or control.
4.These results demonstrate an augmented effect of cholesterol plus methionine in the deterioration of the aortic elastic lamina, and furthermore, the combination of these two agents increases the thickness of the aortic wall. The results indicate a more important role for these two agents in combination than for either agent alone.
Lack of interaction of hyperpnoea with methacholine and histamine in asthma
Authors: SOMPRADEEKUL Suree , HEJAL Rana , McLANE Melissa , LENNER K. A. , NELSON J. A. , McFADDEN E. R. 
Published: August 2015

1.The thermal precipitants of asthma (exercise and hyperventilation) appear to have a unique pathogenesis that does not alter bronchial responsiveness. In the present work, we tested whether hyperpnoea interacts with other constrictor stimuli.
2.To provide data on this issue, we exposed 17 subjects with asthma to isocapnic hyperventilation of frigid air (HV), methacholine (METH) and histamine (HIS) alone and in combination.
3.With HV (mean ventilation = 55.6±7.7 litres/min), METH (2.20±0.7 ;mmol/l) and HIS (10.35±5.04 ;mmol/l) alone, the decrements in forced expiratory volume in 1 ;s (FEV1) from baseline were 27.4±3.4, 27.4±3.8 and 32.4±3% respectively (n = 9). Giving the agonists simultaneously did not produce additive effects (ΔFEV1 HV+METH = 32.8±3.6%; HV+HIS = 28.7±5.1%). None of the individual or combined responses was significantly different from each other. Changing the sequence of the experiments and giving METH at the height of the HV-induced bronchial narrowing, instead of during hyperpnoea, did not alter the findings (n = 8). The maximum fall in FEV1 after both bronchoconstrictors in this experiment (ΔFEV1 = 32.3±4.3%) was not significantly different from either alone (HV = 22.8±1.0%; METH = 27.3±1.9%). When METH and HIS were administered together, however (n = 5), a positive interaction ensued (METH = 1.53±0.56 ;mmol/l, ΔFEV1 = 15.6±4.6%; HIS = 4.77±2.07 ;mmol/l, ΔFEV1 = 18.8±3.1%; METH+HIS ΔFEV1 = 33.4±5.2%; P&lt; 0.001 compared with the individual effects).
4.These results indicate that HV does not interact with stimuli that directly or indirectly modulate airway calibre. It is unclear if this effect represents protection conferred from increased bronchial blood flow or derives from differences in effector mechanisms between the thermal and pharmacological agonists.
Relationship between arterial baroreflex, cardiopulmonary vagal reflex and renal natriuretic response to saline in conscious rabbits
Authors: MAYBAUM Nadine , GORODETSKY Elena , WEINSTOCK Marta 
Published: August 2015

1. We have previously shown that normotensive rabbits with a genetic impairment in arterial baroreflex sensitivity showed a delayed sodium excretion and failed to increase their renal blood flow in response to a saline infusion that did not alter blood pressure. These renal haemodynamic and excretory abnormalities were abolished by renal denervation. The present study determined the sensitivity of the cardiopulmonary baroreceptors and the renal response to a mild saline infusion in normotensive rabbits varying widely in their arterial baroreflex sensitivity.
2. Sensitivity of cardiopulmonary baroreceptors was assessed from the slope of the relationship of the change in both blood pressure and heart rate and the dose of phenylbiguanide, a stimulator of vagal afferents.
3. The change in renal blood flow and lithium and sodium excretion was measured in response to saline, infused at a rate of 0.11 ml·min-1·kg-1 into the ear vein. Urine was collected via a urethral catheter and renal blood flow was measured by para-aminohippurate clearance.
4. A significant correlation was found between the magnitude of the gain of the cardiac arterial baroreflex and the sensitivity of the cardiopulmonary baroreceptor response to phenylbiguanide. The latter was significantly correlated to renal blood flow and lithium clearance 60–90 min after the start of the saline infusion.
5. It was also found that in some normotensive rabbits there was a blunting of cardiovascular regulation as indicated by a reduced sensitivity of cardiopulmonary and arterial baroreceptors. This may explain their abnormal haemodynamic and natriuretic response to salt.
Variation in the apparent sensitivity of the insulin-mediated inhibition of proteolysis to amino acid supply determines the efficiency of protein utilization
Authors: FEREDAY Amelia , GIBSON Neil R. , COX Malcolm , PACY Paul J. , MILLWARD D. Joe 
Published: August 2015

1. The variability between normal individuals in the efficiency of postprandial protein utilization (PPU), a determinant of the apparent protein requirement, was examined in relation to the relative responses of protein synthesis and proteolysis to protein feeding by means of [1–13C]leucine turnover and balance studies.
2. Twenty-five healthy adults were infused intravenously with l-[1-13C]leucine continuously for 9 h. This was started in the postabsorptive state (PA, 3 h) and followed by low-protein feeding (LP, 3 h), and then by isoenergetic high-protein feeding (HP, 3 h). This allowed protein intake to be varied against a constant postprandial insulin level so that the extent of any amino-acid-mediated responses which were additional to those exerted by insulin could be investigated. Leucine oxidation, O, and balance (intake-oxidation), protein synthesis, S, and degradation, D, were calculated from plasma [1-13C]α-ketoisocaproic acid enrichment and 13CO2 excretion.
3. PPUprotein, calculated as change in leucine balance/change in intake (HP-LP), varied from 0.58 to 0.99 (mean = 0.81±0.10), independently of age or sex. PPUprotein varied directly with the inhibition of D and inversely with the increase in leucine concentration and stimulation of O and S.
4. Efficient PPU, as demonstrated by the top quintile of individuals categorized in terms of PPUprotein, involves maximal inhibition of D by protein feeding with minimal increases in free amino acid concentrations, O and S. Lesser inhibition of D and greater stimulation of S and O characterized the lower, less efficient quintile. This indicates that the efficiency of protein utilization in individuals, and a component of their apparent protein requirement, is determined by the sensitivity of the insulin-mediated inhibition of proteolysis to amino acid supply.