bluuebunny/crossref_metadata_2025_split huggingface dataset:
Genetic Variation Associated with Differences in the Response of Plasma Apolipoprotein B Levels to Dietary Fibre
Authors: Hegele Robert A. , Zahariadis George , Jenkins Alexandra L. , Connelly Philip W. , Kashtan Hanoch , Stern Hartley , Bruce Robert , Jenkins David J. A. 
Published: August 2015

1. We hypothesized that differences within genes whose protein products are involved in apolipoprotein B metabolism could influence the response of plasma apolipoprotein B-containing lipoprotein concentrations to increases in dietary fibre.
2. We studied 67 subjects (43 men and 24 women) who had taken part in parallel 2 week metabolic dietary studies involving either wheat bran or oat bran supplementation. Fasting blood lipid, lipoprotein and apolipoprotein concentrations were measured at the start and end of the 2 week metabolic period. Genotypes were determined using DNA markers for the low-density lipoprotein receptor, apolipoprotein B, apolipoprotein CIII and hepatic lipase gene loci.
3. Reductions in plasma concentrations of apolipoprotein B were significantly different depending on genotype determined with a low-density lipoprotein receptor DNA marker (P = 0.03). There was no significant variation in the reduction of plasma total cholesterol, low-density lipoprotein cholesterol or apolipoprotein B concentrations for alleles of other genes tested.
4. Thus, genetic variability is associated with inter-individual differences in the fibre-related reduction in plasma apolipoprotein B and apolipoprotein B-containing lipoprotein concentrations. Implementation of current dietary recommendations to reduce plasma lipoprotein levels with fibre may have variable effects in different individuals in part because of structural differences in candidate genes whose products are involved in lipoprotein metabolism.
Ionized and Total Magnesium Levels in Cyclosporin-Treated Renal Transplant Recipients: Relationship with Cholesterol and Cyclosporin Levels
Authors: Markell M. S. , Altura B. T. , Barbour R. L. , Altura B. M. 
Published: August 2015

1. Ionized magnesium, measured using a newly developed ion-selective electrode, total magnesium, and ionized and total calcium were evaluated in 39 stable, long-term, cyclosporin-treated renal transplant recipients and compared with those of age-matched, non-transplanted control subjects. Total cholesterol, cyclosporin trough level, serum creatinine, time after-transplant and the ratio of ionized calcium to ionized magnesium were also measured in renal transplant recipients and the relationships between these variables and ionized and total magnesium were evaluated.
2. Renal transplant recipients exhibited marked deficits in ionized magnesium, with a mean value of 0.54 ±0.01 mmol/l as compared with 0.61 ± 0.006 mmol/l for normal control subjects (P ≦ 0.05), with a more moderate deficit in total magnesium. Values for ionized and total calcium did not differ. By stepwise linear multiple regression analysis, ionized magnesium was significantly related to cyclosporin trough level and total cholesterol but not to serum creatinine, time after transplant or the dose of cyclosporin. Ionized magnesium correlated inversely with cyclosporin trough level and directly with total cholesterol. The ratio of ionized calcium to ionized magnesium was elevated in renal transplant recipients when compared with control subjects and correlated positively with the cyclosporin trough level.
3. Deficits in ionized magnesium are common during the late post-transplant period in cyclosporin-treated renal transplant recipients. Ionized magnesium may be a more sensitive clinical parameter than total magnesium in this population, in whom total magnesium may be only mildly decreased in the setting of a severe deficit in ionized magnesium.
4. Ionized magnesium correlates with the cyclosporin level. Renal transplant recipients with high cyclosporin levels demonstrate the most severe deficits in ionized magnesium, and this finding could contribute to cyclosporin-induced hypertension and nephrotoxicity. The direct correlation between ionized magnesium and total cholesterol may result from a ‘masked magnesium deficiency’, as has been suggested in animal models, and requires further study. 5. Accelerated atherosclerosis observed after renal transplantation may relate to alterations in ionized magnesium and elevated ratios of ionized calcium to ionized magnesium, which are associated with atherogenesis in other models.
Elevated Serum Superoxide Dismutase Levels Correlate with Disease Severity and Neutrophil Degranulation in Idiopathic Pulmonary Fibrosis
Authors: Borzì Rosa Maria , Grigolo Brunella , Meliconi R. , Fasano L. , Sturani C. , Fabbri M. , Porstmann T. , Facchini A. 
Published: August 2015

1. Tissue damage in idiopathic pulmonary fibrosis is due in part to oxidant-antioxidant imbalance.
2. We evaluated the serum levels of the antioxidant enzyme Cu/Zn superoxide dismutase (EC 1.15.1.1) in 25 patients with idiopathic pulmonary fibrosis, 34 patients with sarcoidosis and 40 healthy control subjects by an enzyme immunometric assay.
3. We found that patients with idiopathic pulmonary fibrosis have higher serum Cu/Zn superoxide dismutase levels than control subjects and patients with sarcoidosis. In addition, serum Cu/Zn superoxide dismutase levels correlate with disease severity indexes in patients with idiopathic pulmonary fibrosis.
4. The increase in serum Cu/Zn superoxide dismutase level in idiopathic pulmonary fibrosis could depend on degranulation of activated neutrophils or release from damaged cells. To elucidate the contribution of neutrophil degranulation we determined the polymorphonuclear cell elastase level in the same specimens. We found a strong correlation between serum Cu/Zn superoxide dismutase and polymorphonuclear cell elastase activities, and, in patients with idiopathic pulmonary fibrosis, we observed higher levels of polymorphonuclear cell elastase than in control subjects and patients with sarcoidosis, which correlated positively with disease severity indexes.
5. Cu/Zn superoxide dismutase can catalyse the dismutation of O2 into H2Oz and generate OH · These oxygen radicals are probably the major factors responsible for tissue damage (in particular, alveolar and endothelial cells) and fibrosis in experimental lung injury.
6. Taking into account: (a) the specific enzymic activity of Cu/Zn superoxide dismutase (i.e. production of H2O2 and OH ·), (b) the possible enhancement of the effect of reduced glutathione deficiency (high H2O2) by increased Cu/Zn superoxide dismutase activity, and (c) the correlation that we found between disease severity and Cu/Zn superoxide dismutase and polyphorphonuclear cell elastase levels, we suggest that, in idiopathic pulmonary fibrosis, increased activities of Cu/Zn superoxide dismutase and polymorphonuclear cell elastase can achieve a pro-inflammatory pathogenic effect.
7. However, the results of this study of serum Cu/Zn superoxide dismutase and polymorphonuclear cell elastase concentrations in individual patients does not support a clear-cut cause-effect relationship between these enzyme levels and the clinical changes in the patients.
Vasodilatory Action of the Calcium Antagonist Amlodipine on Large and Resistance Pulmonary Arteries from Normoxic and Chronically Hypoxic Rats
Authors: Woodmansey Paul A. , Zhang Fan , Channer Kevin S. , Morice Alyn H. 
Published: August 2015

1. Isolated rat aorta and pulmonary arteries were maximally precontracted with 100 mmol/l KCl, and the vasorelaxation due to the dihydropyridine calcium antagonist amlodipine was measured. The response of large pulmonary arteries (mean lumen diameter 983 μm) was directly compared with that of isolated pulmonary resistance vessels (mean lumen diameter 259 μm) from both normoxic animals and animals exposed to chronic hypoxia.
2. Amlodipine caused a significant relaxation of aorta (P &lt;0.001). A significant relaxation of large and resistance pulmonary arteries from both normoxic and chronically hypoxic animals was also demonstrated at all doses tested (P &lt;0.05) or less).
3. Amlodipine produced significantly more relaxation in pulmonary resistance vessels than in large pulmonary arteries from both normoxic and chronically hypoxic rats (P &lt;0.02).
4. The action of amlodipine was slow in onset and persistent in all vessels studied. In the pulmonary vessels from normoxic animals both the rate of onset and the magnitude of effect was proportional to the drug concentration (P &lt;0.001).
5. These results demonstrate that amlodipine is a potent inhibitor of KCl-induced contractions in rat pulmonary arteries with a preferential action in pulmonary resistance vessels.
Expression of the Three Endothelin Genes and Plasma Levels of Endothelin in Pre-Eclamptic and Normal Gestations
Authors: McMahon L. P. , Redman C. W. G. , Firth J. D. 
Published: August 2015

1. Maternal vasoconstriction and fetal growth retardation are part of the syndrome of pre-eclampsia and are thought to be related to placental insufficiency. There is evidence to suggest that the powerfully vasoactive endothelin peptides might be involved in the pathogenesis.
2. The production of endothelins appears to be regulated mainly by modulation of mRNA levels, and they are thought to exert their effects locally, rather than systemically. Hence, the measurement of endothelin mRNA levels in tissues would be expected to reflect the activity of the endothelin systems.
3. RNAase protection assays, using specific antisense probes capable of distinguishing between the endothelin mRNA isoforms, have been used to examine the expression of the three endothelin genes in placental villous tissue, amniotic membrane and myometrium. Samples were taken from 15 pre-eclamptic women and from 14 women with normal gestations. Myometrium was taken at hysterectomy from five non-pregnant women as an additional control. Plasma concentrations of immunoreactive endothelin [endothelin-1, endothelin-2 and big endothelin (not distinguished)] were measured in samples taken concurrently from uterine vein and peripheral blood during surgery in ten patients.
4. The level of endothelin-1 mRNA in placental villous tissue was significantly higher in pre-eclamptic women (32 weeks gestation) than in control subjects (38 weeks gestation) (1.85 +0.26 versus 0.52 +0.09 arbitrary units, means + SEM, P &lt;0.001) and in gravid than in non-gravid myometrium (P &lt;0.001). Endothelin-2 was not expressed in villous tissue, but was expressed in amniotic membrane and myometrium, with relatively little difference between preeclamptic and control groups. Endothelin-3 was expressed at very low levels in all tissues examined.
5. The concentration of immunoreactive endothelin was higher in uterine than in peripheral vein blood in samples which were taken simultaneously (9.0 +1.2 versus 5.6 +0.7 pmol/l, P &lt;0.05). Levels were not significantly different in pre-eclamptic and control groups.
6. Endothelin-1 gene expression is increased in placental villous tissue of pre-eclamptic gestations, possibly contributing to placental vasoconstriction/vascular insufficiency and hence fetal growth retardation in this disease.
Concentration-Dependent Effects of Insulin on Ca2+ Influx in Vascular Smooth Muscle Cells of Normotensive and Spontaneously Hypertensive Rats
Authors: Zhu Zhiming , Tepel Martin , Neusser Marcus , Mehring Norbert , Zidek Walter 
Published: August 2015

1. The effect of insulin on cytosolic free Ca2+ concentration was measured using fura-2 in vascular smooth muscle cells of normotensive and spontaneously hypertensive rats.
2. In both strains, insulin increased cytosolic free Ca2+ concentration in a concentration range between 10−6 and 10−3 units/ml. The maximum increase in cytosolic free Ca2+ concentration was observed with 10−5 units/ml insulin (107 +25 and 82+27 nmol/l in spontaneously hypertensive rats and normotensive rats, respectively).
3. The effect of insulin was dependent on extracellular Ca2+ and was enhanced by stimulation of protein kinase C.
4. Thus insulin appears to induce a Ca2+ influx in vascular smooth muscle cells only over a certain range of concentrations. No significant difference in the response to insulin of cells from normotensive and hypertensive rats was observed.
Acetyl-CoA:lyso-Platelet-Activating Factor Acetyltransferase Activity in Neutrophils from Asthmatic Patients and Normal Subjects
Authors: Misso Neil L. A. , Gillon Robyn L. , Taylor Marcia L. , Stewart Geoffrey A. , Thompson Philip J. 
Published: August 2015

1. Platelet-activating factor is a putative mediator of inflammation in asthma and the enzyme acetyl-CoA:lyso-platelet-activating factor acetyltransferase appears to be important in regulating platelet-activating factor production by leucocytes. To determine whether there are differences in acetyl-transferase activity between asthmatic patients and normal subjects, enzyme activity was assayed in neutrophil lysates from atopic asthmatic patients (n = 20), aspirin-sensitive asthmatic patients (n = 12) and healthy, non-atopic, non-asthmatic control subjects (n = 20), both basally and after stimulation with the calcium ionophore A23187.
2. For a range of acetyl-CoA concentrations, acetyl-transferase activity (nmol of [acetyl-3H]PAF min−1 mg−1 of protein) in unstimulated neutrophils from atopic asthmatic patients was significantly higher than that for normal subjects (P = 0.038) and the mean Vmax. for atopic asthmatic patients [18.4 (SD 6.9) nmol min−1 mg−1 of protein] was significantly greater than that for the control subjects [14.9 (SD 4.6) nmol min−1 mg−1 of protein P &lt;0.05]. The mean Vmax. for aspirin-sensitive asthmatic patients [15.9 (SD 6.9) nmol min−1 mg−1 of protein] was not significantly different from that for the normal subjects.
3. The mean ratio Vmax. stimulated/ Vmax. unstimulated for acetyltransferase from atopic asthmatic patients (1.71, SD 0.45) was significantly less than that for the normal subjects (2.13, SD 0.63, P &lt;0.05), suggesting that acetyltransferase from atopic asthmatic patients was less sensitive to stimulation with A23187 in vitro. The mean ratio Vmax. stimulated/ Vmax. unstimulated for aspirin-sensitive asthmatic patients (2.05, SD 0.71) was not significantly different from that for the normal subjects.
4. Vmax. stimulated was significantly correlated with Vmax. unstimulated in atopic asthmatic patients (P = 0.0001) and aspirin-sensitive asthmatic patients (P = 0.012), but not in normal subjects (P = 0.071).
5. These results suggest that, in atopic asthmatic patients, neutrophils may be subject to chronic priming in vivo for increased acetyltransferase activity and capacity for platelet-activating factor synthesis. In these patients the increased platelet-activating factor production may be contributing significantly to the degree of inflammation associated with their asthma.
Effect of Chronic Low-Dose Arginine Vasopressin Infusion on Body Fluid Homoeostasis during Adaptation from a High-to a Low-Sodium Diet in Normal Man
Authors: Sutters M. , Carmichael D. J. S. , Lightman S. L. , Peart W. S. 
Published: August 2015

1. A diuresis occurs within the first 36 h of salt restriction. A decline in plasma arginine vasopressin concentration may contribute to both the diuresis and antinatriuresis.
2. We have studied six normal human subjects during 36 h of dietary sodium restriction. In one study subjects received an intravenous infusion of D-glucose, and in the other an infusion of arginine vasopressin (6 fmol min−1 kg−1).
3. In the D-glucose phase plasma arginine vasopressin concentration fell (1.77 +034 to 1.02 +0.13 pg/ml), urine flow increased (67.9 +113 to 89.8 + 17.1 ml/h), haemoconcentration occurred (packed cell volume 40.8 +0.3 to 42.8 +03%, protein concentration 71.6 +03 to 74.5 + 0.6 g/l), plasma sodium concentration fell (140 +0.2 to 138 +0.2 mmol/l) and plasma renin activity increased (1600+153 to 3700 + 356 pg of angiotensin I h−1 ml−1).
4. In the arginine vasopressin phase plasma arginine vasopressin concentration remained constant (13 + 0.13 to 134 +0.11 pg/ml), the diuresis was reversed (65.7 +9.9 to 52.1 +8.9 ml/h), plasma sodium concentration fell further (139.8 +0.4 to 136.1 +0.4 mmol/l), the rise in plasma renin activity was reduced (arginine vasopressin 2552 + 292; D-glucose, 3700 + 356 pg of angiotensin I h−1 ml−1) and creatinine clearance was lower in the last 12 h of salt restriction (arginine vasopressin, 96.1 +6.9; D-glucose 116.5 + 6.8 ml/min). Renal sodium excretion was unaffected by arginine vasopressin infusion.
5. We conclude that the fall in plasma arginine vasopressin concentration during dietary salt restriction, whilst not affecting renal sodium excretion, may be important in the regulation of plasma sodium concentration, plasma renin activity and glomerular filtration.
Determinants of the Renal Clearance of Exogenous Lithium in a Large Sample of a White Male Working Population
Authors: Cappuccio Francesco P. , Strazzullo Pasquale 
Published: August 2015

1. The associations between the renal clearance of ingested lithium (used as a marker of renal proximal tubular sodium handling) and a number of biological variables have been investigated in an unselected sample of 592 healthy and untreated white men (aged 21–68 years) under their usual living conditions and drawn from a population at work.
2. Renal excretion of lithium was expressed both as clearance of lithium and as fractional excretion of lithium, i.e. normalized for unit of glomerular filtrate.
3. Clearance of lithium was positively associated with a number of anthropometric variables such as weight (r = 0.215; P &lt;0.001), height (r = 0.212; P &lt;0.001), body mass index (r = 0.122; P &lt;0.01) and body surface area (r = 0.244; P &lt;0.001). However, when expressed as fractional excretion of lithium many of these associations were lost or tended to be negative (weight, r = −0.107, P &lt;0.01; body mass index, r = −0.119, P &lt;0.01), greatly depending on the strong relationship between body size and/or mass and glomerular filtration rate. The associations between clearance of lithium and other renal variables reflected, in part, a spurious association mediated by the common relationship with glomerular filtration rate. However, when expressed as fractional excretion of lithium, only some associations were apparent (fractional excretion of sodium, r = 0.256, P &lt;0.001; fractional excretion of uric acid, r = 0.336; P &lt;0.001), probably indicating some plausible biological relationships. These results were confirmed by analysis of co-variance by quintiles of clearance of lithium and fractional excretion of lithium.
4. The results of the present study show that the renal excretion of ingested lithium (an approximate index of proximal tubular sodium handling in man) could be used in an epidemiological setting. However, the use of the fractional excretion of lithium rather than the clearance of lithium as such would be advisable to remove the confounding effects of age and anthropometry, at least in a white middle-aged male working population.
Tumour Necrosis Factor-α, Resting Energy Expenditure and Cachexia in Cystic Fibrosis
Authors: Elborn J. Stuart , Cordon Sally M. , Western Philip J. , MaCdonald Ian A. , Shale Dennis J. 
Published: August 2015

1. We investigated the relationship between circulating tumour necrosis factor-α concentrations, resting energy expenditure, cachexia and altered intermediary metabolism in patients with cystic fibrosis and chronic pulmonary infection.
2. Twenty adult patients with cystic fibrosis and chronic bronchial sepsis covering a spectrum of severity of lung disease (forced expiratory volume in 1 s 30–100% of predicted) were compared with 10 age matched, healthy, non-cystic fibrosis subjects.
3. Circulating tumour necrosis factor-α, C-reactive protein and neutrophil elastase-α1-antiproteinase complex concentrations were determined simultaneously with glycerol, non-esterified fatty acids, catecholamines, anthropometric indices and resting energy expenditure (ventilated hood method).
4. Weight, body mass index and arm muscle mass were reduced in patients with cystic fibrosis compared with healthy control subjects (P &lt;0.01), whereas mean resting energy expenditure was increased [121 versus 101% predicted, mean difference 19.2% (95% confidence interval 11.0-27.4%), P &lt;0.001]. Circulating concentrations of glycerol (P &lt;0.01), non-esterified fatty acids (P &lt;0.01), adrenaline (P &lt;0.05), tumour necrosis factor-α, C-reactive protein and neutrophil elastase-α1-antiproteinase complex (P &lt;0.01) were increased in patients compared with control subjects [tumour necrosis factor-α 96.9 versus 24.7 pg/ml, mean difference 72.2 pg/ml [95% confidence interval 27.7-116.7 pg/ml), P &lt;0.001]. Resting energy expenditure was significantly related to tumour necrosis factor-α levels and forced expiratory volume in 1 s.
5. In patients with cystic fibrosis and chronic pulmonary sepsis changes in resting energy expenditure, body composition and intermediary metabolism are consistent with the systemic effects of the host inflammatory response, which may be responsible for cachexia in adult patients. In particular these changes are consistent with the action of tumour necrosis factor-α, which was detected in the circulation during a period of apparent clinical stability.
Rat Renal, Aortic and Pulmonary Endothelin-1 Receptors: Effects of Changes in Sodium and Water Intake
Authors: Michel Harald , Bäcker Angela , Meyer-Lehnert Harald , Migas Iris , Kramer Herbert J. 
Published: August 2015

1. In the present study we investigated, first, the effects of high Na+ intake and, second, the effects of water deprivation on plasma endothelin-1 concentration and urinary endothelin-1 excretion and on endothelin receptors in membranes of renal glomeruli and papillae and of aortic smooth muscle and lung tissue from 32 female Sprague-Dawley rats.
2. After 5 weeks of high Na+ intake (n = 8) urinary Na+ excretion was 10.5 + 1.3 compared with 1.6 + 0.2 mmol/24h in controls. Body weight, plasma osmolality, plasma endothelin-1 concentration (23 + 6 versus 28 + 3 fmol/ml) and urinary endothelin-1 excretion (6.1 + 13 versus 4.7 + 0.3 pmol/24 h) remained unchanged.
3. The characteristics of endothelin-1 receptors in glomeruli, papillae, aortic smooth muscle and lung tissue from salt-loaded rats were not different from those of controls.
4. After 48 h water deprivation (n = 8) body weight had decreased, whereas packed cell volume and plasma and urine osmolalities had increased compared with controls (n = 8) (P &lt;0.05). Plasma endothelin-1 concentration (40 + 6 versus 21 + 2 fmol/ml) was higher (P &lt;0.01) and urinary endothelin-1 excretion (1.0 + 0.2 versus 2.8 + 03 pmol/24 h) was lower than in controls (P &lt;0.01).
5. Water deprivation was accompanied by increases in endothelin-1 binding sites in glomeruli (Bmax. 4.8 + 0.4 versus 3.6 + 0.2 pmol/mg of protein; P &lt;0.05) with unchanged receptor affinity (Kd 56 + 9 versus 57 + 8 pmol/l), in papillae (Bmax. 8.0 + 0.7 versus 6.2 + 0.5 pmol/mg of protein; P &lt;0.05) with unchanged Kd (78 + 6 versus 63 + 4 pmol/l) and in aortic smooth muscle cells (Bmax. 3.5 + 0.2 versus 2.8 + 0.2 pmol/mg of protein; P &lt;0.05) in which Kd rose to 307 + 27 versus 180 + 22 pmol/l (P &lt;0.05). Endothelin-1 receptors in lung tissue were unaltered (Bmax. 10.0 + 03 versus 103 + 0.8 pmol/mg of protein; Kd 152 + 12 versus 137 + 14 pmol/l).
6. Our results suggest that the peripheral endothelin-1 system may play a role in the adaptation to changes in body water content rather than in Na+ balance.