bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effects of Leg Muscle Pumping and Tensing on Orthostatic Arterial Pressure: A Study in Normal Subjects and Patients with Autonomic Failure
Authors: Ten Harkel A. D. J. , Van Lieshout J. J. , Wieling W. 
Published: August 2015

1. The effects of leg muscle pumping (tiptoeing) and tensing (leg-crossing) on orthostatic blood pressure were investigated in six healthy adult subjects (aged 28–34 years) and in seven patients with severe hypoadrenergic orthostatic hypotension (aged 20–65 years).
2. Finger arterial pressure was monitored. Relative changes in left ventricular stroke volume were computed by a pulse contour method.
3. Tiptoeing increased mean arterial pressure (7 ± 5 mmHg) in the healthy subjects, but not in the patients, whereas cardiac output increased in both groups, although by more in the healthy adults than in the patients (35 ± 10% versus 20 ± 11%, P &lt; 0.05). Systemic vascular resistance decreased substantially in both groups while tiptoeing. Leg-crossing did not affect arterial pressure in the healthy subjects, although stroke volume had increased. In contrast, in the patients an increase in cardiac output (16 ± 12%) and mean blood pressure (13 ± 13 mmHg) was observed.
4. Tiptoeing and leg-crossing have different effects on orthostatic blood pressure in healthy adult subjects and in patients with autonomic failure. In normal humans, tiptoeing increases arterial pressure, whereas leg-crossing has little effect. In the patients, in contrast, tiptoeing has little effect, whereas leg-crossing increases arterial pressure considerably. Patients with autonomic failure should be instructed to apply leg-crossing to combat orthostatic dizziness.
Aspirin Does Not Affect the Flow Cytometric Detection of Fibrinogen Binding to, or Release of α-Granules or Lysosomes from, Human Platelets
Authors: Chronos Nicolas A. F. , Wilson Darren J. , Janes Sarah L. , Hutton Ronald A. , Buller Nigel P. , Goodall Alison H. 
Published: August 2015

1. Aspirin inhibits the conversion of arachidonic acid to thromboxane A2 which reinforces the effects of weak agonists such as ADP in platelets.
2. In this study the effect of aspirin (300 mg/day) on platelet agonist response was measured by whole blood flow cytometry of unfixed blood samples from normal subjects (n = 10), an assay that investigates aggregation-independent changes in the platelet.
3. Fibrinogen binding to unstimulated platelets or to platelets stimulated with ADP or thrombin was unaffected by aspirin.
4. Under the conditions of this assay, platelets undergo a partial degranulation of α-granules and lysosomes (evidenced by expression of P-selectin and CD63, respectively) in response to ADP, and full degranulation in response to thrombin. P-selectin expression was paralleled by release of β-thromboglobulin. None of these events was affected by aspirin.
5. Thromboxane formation was totally prevented by the aspirin treatment, as shown by Born aggregometry in which the platelet aggregatory response to arachidonic acid was abolished and secondary aggregation by ADP was inhibited.
6. The flow cytometric assay can therefore be used to investigate platelets in patients, regardless of aspirin therapy.
7. These findings suggest that platelet fibrinogen binding and the release of platelet α-granule and lysosomal contents, in response to stimulation with physiological agonists, can continue in patients despite aspirin therapy. This may help to explain why aspirin is only partially effective in preventing thrombotic events.
Impaired Left Ventricular Relaxation and Arterial Stiffness in Patients with Essential Hypertension
Authors: Chang K.-C. , Tseng Y. Z. , Kuo T. S. , Chen H. I. 
Published: August 2015

1. This study was designed to determine how left ventricular relaxation function in patients with essential hypertension is impaired by arterial haemodynamic load that is increased in early ejection phase. These patients did not suffer from cardiac hypertrophy or disturbed coronary perfusion. We used a high-fidelity multisensor catheter to record pressure and flow signals in the ascending aorta. The timing and magnitude of wave reflection were obtained by decomposing the measured waves into their forward and backward components. Radionuclide angiography was employed to obtain the time-activity curve. The left ventricular relaxation function was assessed by analysing the time-activity curve, which was filtered using Fourier expansion with the number of harmonics for minimum error.
2. In comparison with age-matched normotensive subjects (seven subjects with mean blood pressure 97 mmHg), hypertensive subjects (seven subjects with mean blood pressure 138 mmHg) had a shorter backward wave arrival time (193 ± 26 versus 258 ± 35 ms) and a higher reflection factor (0.58 ± 0.12 versus 0.42 ± 0.07). Isovolumic relaxation period was prolonged in hypertensive subjects (118 ± 19 versus 90 ± 19 ms). There was an inverse correlation between isovolumic relaxation period and backward wave arrival time in all 14 subjects (r = −0.67, P &lt; 0.05). In contrast, there were no significant differences in cardiac output and time to peak ejection rate between the two groups.
3. Our analyses revealed that early return of the enhanced wave reflection may profoundly impair left ventricular relaxation function in patients with hypertension. The prolonged isovolumic relaxation and unaltered cardiac output suggested that relaxation abnormalities may have a tendency to precede systolic dysfunction in our hypertensive subjects.
α1-Antitrypsin Phenotypes in Patients with Anti-Neutrophil Cytoplasmic Antibody-Positive Vasculitis
Authors: Lhotta Karl , Vogel Wolfgang , Meisl Thomas , Buxbaum Martina , Neyer Ulrich , Sandholzer Christoph , König Paul 
Published: August 2015

1. The genetic background of anti-neutrophil cytoplasmic antibody (ANCA)-associated systemic vasculitis remains largely unknown. Recently a very high prevalence of medium and severe deficiency of α1-antitrypsin was described in a small group of patients with Wegener's granulomatosis and c-ANCA. c-ANCAs are autoantibodies against proteinase 3, and α1-antitrypsin is the main inhibitor of this enzyme.
2. α1-Antitrypsin phenotypic polymorphism was determined by isoelectric focusing in 32 patients with c-ANCA-associated systemic vasculitis. Twenty-nine patients had Wegener's disease, two had microscopic polyarteritis and one suffered from idiopathic rapidly progressive glomerulonephritis.
3. Two patients were homozygous PiZZ and three were heterozygous PiMZ. These phenotype frequencies differed significantly from expected values, assuming Hardy-Weinberg equilibrium (P &lt; 0.01). Compared with a control group of 868 healthy blood donors, these results meant a significant increase in the PiZ allele (0.0138 versus 0.1094, P&lt; 0.001).
4. Furthermore, the serum of 47 patients with severe α1-antitrypsin deficiency (PiZZ) was tested for the presence of ANCA. All sera were negative for c-ANCA and p-ANCA. None of the patients showed clinical signs of systemic vasculitis.
5. In conclusion, these data indicate that α1-antitrypsin deficiency, despite being significantly more common in patients with c-ANCA-associated systemic vasculitis, is only a minor genetic risk factor for the development of this disease.
Production of Acute Gastric Erosions in the Cat by Individual Human Pepsins
Authors: Sacra P. , Roberts N.B. , Taylor W.H. 
Published: August 2015

1. Differing amounts of human pepsins 1, 3 (pepsin A) and 5 (pepsin C or gastriscin) in aqueous HCl/NaCl at pH 1.3 were placed in Perspex rings on the exposed luminal surface of the perfused cat stomach to test for mucolytic and erosive activity in vivo, with the acid medium in control rings.
2. After incubation at 37°C for 60 or 120 min, the test and control solutions were replaced by the same volume of each test or control solution containing 18 mg of aspirin and incubated for a further 120 min.
3. The number of bleeding points or erosions was counted at 15 min intervals. None was observed with human pepsins 1, 3 and 5 or with pig pepsin A or in the control rings.
4. With aspirin, erosions developed in all ringed areas. Their rate of development with time for pepsin 1 and pig pepsin did not differ from controls. Significantly more erosions developed with human pepsins 3 (5 mg per ring, P &lt; 0.001) and 5 (0.32 mg per ring, P &lt; 0.05).
5. Human pepsins 3 and 5, applied at pH 1.3 to the mucosal surface of the perfused cat stomach, therefore cause erosions when administered with aspirin, but do not produce erosions when given alone. In man, pepsins secreted in increased amount or concentration may therefore be unlikely to cause significant mucosal erosion unless human gastric mucosa is less resistant to pepsins than cat mucosa. Pepsins may perhaps facilitate the action of a second factor, such as aspirin, or infection with Helicobacter pylori.
Spectral Analysis of Systolic Blood Pressure and Heart Rate after Heart Transplantation in Children
Authors: Constant Isabelle , Girard Arlette , Bidois Jérôme Le , Villain Elizabeth , Laude Dominique , Elghozi Jean-Luc 
Published: August 2015

1. The aim of the study was to examine the short-term variability in blood pressure and heart rate in 19 children who had received heart transplants and in eight normal control children.
2. Blood pressure was determined by a finger arterial pressure device. We examined the power spectra for heart rate and systolic blood pressure in the supine and tilted positions. In addition, we studied the acute changes in blood pressure and heart rate during active standing.
3. In the transplanted children we could distinguish two groups (groups A and B) in whom heart rate variability differed, although in both it was greatly reduced compared with controls (group C). In group A there were no significant fluctuations in the mid-frequency range for heart rate. The gain of the relationship between systolic blood pressure and heart rate was very low and there were virtually no heart rate changes associated with passive tilting.
4. By contrast, in group B transplant patients the heart rate variability, as assessed by standard deviation, was about half that of normal controls. The power spectra attenuation was greater in the high-frequency than in the mid-frequency bands. On passive tilting the latter became enhanced, but not the high-frequency variability. On active standing the tachycardic response was about half that of controls. The findings suggest some reinnervation involving cardiac sympathetic fibres to a greater degree than the fast-responding vagal fibres.
5. In both groups A and B the drop in systolic blood pressure observed early in active standing was about 4–6 times as great as in controls. One possible mechanism could be the loss of cardiac afferents.
6. Time since operation was a critical factor for reinnervation, since all subjects from group B were transplanted more than 44 months prior to the recording.
7. We conclude that in a proportion of children who have received heart transplantation there is a delayed reinnervation of the heart, which probably involves sympathetic effectors rather than the vagus.
Nitric Oxide Synthase Activity is Increased in Patients with Sepsis Syndrome
Authors: Goode Helen F. , Howdle Peter D. , Walker Barry E. , Webster Nigel R. 
Published: August 2015

1. We measured nitric oxide synthase activity in peripheral blood polymorphonuclear leucocytes from 10 patients with sepsis syndrome and 10 healthy subjects.
2. Synthase activity was significantly higher in patients with sepsis than in control subjects (1202 ± 579 compared with 595 ± 544 pmol of nitric oxide min−1 mg−1 of cell protein, P &lt; 0.05).
3. Activity was greatest in those patients with the larger number of organ failures, although this failed to reach significance (1489 ± 560 in patients with three or more organ failures and 843 ± 404 pmol of nitric oxide min−1 mg−1 of cell protein in those with less than three, P = 0.11).
4. This study provides evidence for the role of overproduction of the vasodilator nitric oxide in sepsis syndrome.
Production of Eicosanoids and Cytokines by Kupffer Cells from Young and Old Rats Stimulated by Endotoxin
Authors: Brouwer A. , Parker S. G. , Hendriks H. F. J. , Gibbons L. , Horan M. A. 
Published: August 2015

1. The clinicopathological features of endotoxaemia have been ascribed to cytotoxic mediators such as tumour necrosis factor, interleukins and eicosanoids. Macrophages, particularly Kupffer cells, are an important source of these mediators. Mortality from endotoxaemia is highly age related.
2. These studies focus on the role of hepatic Kupffer cells in the increased sensitivity of old rats to bacterial endotoxins. Possible age-related changes in the production of eicosanoids and induction of gene expression and secretion of interleukin 1, tumour necrosis factor and interleukin 6 were investigated in Kupffer cells derived from both young and old animals.
3. Basal production of biological response modifiers was low in cells of both young and old rats. Lipopolysaccharide stimulated production of the same types of monokines as described for other types of macrophages, although the pattern was specific for Kupffer cells.
4. Eicosanoids, predominantly prostaglandin D2 and prostaglandin F2α, were produced mainly during the first hour after exposure to lipopolysaccharide. Endotoxin stimulated synthesis of mRNAs of interleukin 1, interleukin 6 and tumour necrosis factor α resulting in increased secretion of these cytokines into the medium.
5. Kupffer cells from both young and aged animals appear to be exquisitely sensitive to endotoxin in respect of expression of mRNA for both interleukin 1α and interleukin 1β and less sensitive with respect to interleukin 6 and tumour necrosis factor α gene expression. At relatively high lipopolysaccharide concentrations interleukin 6 was secreted in particularly large amounts.
6. The effects of ageing on any of these responses of Kupffer cells were minimal.
7. It seems unlikely that age-related changes in the synthesis and secretion of eicosanoids and cytokines by Kupffer cells are an important factor in the increased susceptibility of old rats to LPS.
Increased Hepatic Secretion of Very-Low-Density Lipoprotein Apolipoprotein B-100 in Obesity: A Stable Isotope Study
Authors: Cummings Michael H. , Watts Gerald F. , Pal Cauvery , Umpleby Margot , Hennessy Thomas R. , Naoumova Rossitza , Sönksen Peter H. 
Published: August 2015

1. We measured the hepatic secretion of very-low-density lipoprotein apolipoprotein B-100 (VLDL apoB) using a stable-isotope gas chromatography—mass spectrometry method in six obese subjects [three males, three females, age 41.5 ± 3.4 years (mean ± SEM), weight 105.0 ± 4.8 kg, plasma total cholesterol concentration 6.2 ± 0.4 mmol/l, triacylglycerol 2.8 ± 0.8 mmol/l, high-density lipoprotein cholesterol 1.0 ± 0.2 mmol/l] and six lean control subjects (three males, three females, age 41.8 ± 3.7 years, weight 68.2 ± 4.9 kg, total cholesterol concentration 4.5 ± 0.3 mmol/l, triacylglycerol 0.8 ± 0.2 mmol/l, high-density lipoprotein cholesterol 1.3 ± 0.1 mmol/l).
2. Plasma total cholesterol, triacylglycerol and mevalonic acid (an index of cholesterol synthesis in vivo) concentrations were significantly higher in the obese subjects than in control subjects (P = 0.02, P = 0.03, P = 0.04, respectively). VLDL apoB pool size and absolute secretion rate were significantly higher in the obese subjects than in control subjects (323.4 ± 99.8 mg versus 53.6 ± 17.1 mg, P = 0.004; and 42.3 ± 13.8 mg kg fat-free mass−1 day−1 versus 10.7 ± 0.4 mg kg fat-free mass−1 day−1, P = 0.01), but there was no significant difference in the fractional catabolic rate of VLDL apoB.
3. After pooling obese and control data, there was a significant positive association between VLDL apoB absolute secretion rate and (i) fat mass (r = 0.71, P = 0.009), (ii) plasma total cholesterol (r = 0.66, P = 0.019), (iii) triacylglycerol (r = 0.72, P = 0.008), (iv) total apolipoprotein B-100 (r = 0.77, P = 0.02), (v) mevalonic acid (r = 0.81, P &lt; 0.001), (vi) fasting insulin (r = 0.61, P = 0.03) and (vii) fasting C-peptide (r = 0.70, P = 0.01) concentrations. There was also a significant positive association between plasma insulin and plasma mevalonic acid concentrations (r = 0.59, P = 0.04). The association between VLDL apoB absolute secretion rate and plasma mevalonic acid concentration remained significant after adjusting for plasma insulin concentration (r = 0.83, P = 0.01); however plasma insulin concentration was no longer associated with VLDL apoB absolute secretion rate (P = 0.40).
4. We conclude that increased hepatic secretion of VLDL apoB contributes to the elevated lipid concentrations observed in obesity. We suggest that increased secretion of this apolipoprotein may be a consequence of resistance to the inhibitory effect of insulin on VLDL apoB secretion and may be partly mediated by increased cholesterol synthesis.
Acute Stimulation of Albumin Synthesis Rate with Oral Meal Feeding in Healthy Subjects Measured with [Ring-2H5]Phenylalanine
Authors: Hunter K. A. , Ballmer P. E. , Anderson S. E. , Broom J. , Garlick P. J. , McNurlan M. A. 
Published: August 2015

1. The short-term effect of oral feeding on albumin synthesis rate was investigated in 12 healthy volunteers using two meal regimens. Albumin synthesis was measured over 90 min after injection of a ‘flooding’ amount (43 mg/kg body weight) of phenylalanine enriched to 7.5, 10 or 15 atoms% with the stable isotope [ring-2H5]phenylalanine.
2. In one set of subjects, consumption of five small hourly meals resulted in a consistent and significant increase (P &lt; 0.05) in albumin fractional synthesis rate from a mean (± SEM) fasting value of 5.8 (± 0.4)%/day to 7.1 (± 0.4)%/day in the fed state.
3. A second study in which albumin synthesis was measured 30 min after consumption of a single larger meal was carried out in another set of volunteers. The fractional rate of albumin synthesis was again significantly elevated after feeding (P &lt; 0.05), rising from 7.1 (± 0.4)%/day in the fasted state to 9.1 (± 0.6)%/day in the fed state. In both studies, similar responses were observed in the absolute rate of albumin synthesis (mg day−1 kg−1).
4. Albumin secretion time was significantly shorter (P &lt; 0.05) after feeding in both studies, suggesting that the acute stimulation in albumin synthesis observed after feeding may in part be mediated via a post-transcriptional mechanism.
5. The response of total liver protein synthesis to oral feeding was investigated in an animal model employing adult rats studied with a flooding amount of [2,6-3H]phenylalanine.
6. The results indicated a stimulation of 20% with no difference in the proportion of albumin synthesis relative to total liver synthesis, determined from the immunoprecipitation of albumin from the liver.
Effects of Insulin-Like Growth Factor-1 and Growth Hormone on the Net Flux of Amino Acids across the Hind Limbs in the Surgically Traumatized Pig
Authors: Malmlöf Kjell , Cortova Zuzana , Saxerholt Henri , Karlsson Eivor , Arrhenius-Nyberg Vibeke , Skottner Anna 
Published: August 2015

1. After surgery three groups of six female pigs weighing on average 52.2 kg (SD 3.5) received vehicle, recombinant insulin-like factor-1 (364.4 μg day−1 kg−1) or recombinant human growth hormone (467.7 m-i.u. day−1 kg−1) for two post-operative days. Vehicle and peptides were infused intravenously together with total parenteral nutrition providing 129 kJ day−1 kg−1 non-protein calories and 0.35 gN day−1 kg−1.
2. On both post-operative days the mean concentration of insulin-like growth factor-1 in arterial blood samples was clearly below presurgical levels in animals receiving vehicle or recombinant human growth hormone, whereas recombinant human insulin-like growth factor-1 infusions more than restored insulin-like growth factor-1 concentrations. These last samples, however, contained significantly (P&lt;0.05) less insulin than those from other animals.
3. Infusion of recombinant human growth factor was often associated with higher circulating levels of amino acids compared with recombinant human insulin-like growth factor-1 infusions. Despite this, both hormones significantly (P &lt; 0.05) increased the hind limb net balance of total amino acids on postoperative day 1. Net balances of −44.2, +69.5 and +100.9 μmol/min (pooled SE 35.3) were associated with infusion of vehicle, recombinant human insulinlike growth factor-1 and recombinant human growth hormone respectively. This response was also closely reflected in the group of non-essential amino acids.
4. The net efflux of alanine from the hind limbs was also significantly (P &lt; 0.002) reduced, whereas glutamine was less affected.
5. On post-operative day 2, there was a general drop in cortisol and urea levels, implying a loss of catabolic tone. Concomitantly, most effects seen on amino acids flux after hormone administration on the previous day disappeared.
6. It is concluded that, in the acute catabolic state, both recombinant human insulin-like growth factor-1 and recombinant human growth hormone can prevent the erosion of body protein by increasing the peripheral net balance of amino acids and can thus increase the efficacy of total parenteral nutrition.
Effects of Low-dose Angiotensin II Infusion on Loop Segment Reabsorption: A Free-Flow Micropuncture Study in Rats
Authors: Fransen René , Boer Walther H. , De Roos Remmert , Boer Peter , Koomans Hein A. 
Published: August 2015

1. Little direct information is available on the actions of angiotensin II beyond the proximal tubule. We therefore studied the effect of a mildly vasoconstrictive dose of angiotensin II on tubular handling of water, sodium (Na+) and lithium (Li+) in rats by means of free-flow micropuncture at the late proximal tubule and the early distal tubule.
2. Endogenous angiotensin II was suppressed by pretreament with enalapril. Compared with a control group, angiotensin II increased mean arterial pressure by 15 mmHg. Glomerular filtration rate decreased from 1.32 ± 0.05 to 1.10 ± 0.05 ml/min, Na+ excretion from 0.43 ± 0.09 to 0.13 ± 0.03 μmol/min, fractional delivery of water at the late proximal tubule from 50.1 ± 1.7 to 42.9 ± 3.2%, fractional delivery of Na+ at the late proximal tubule from 46.5 ± 1.3 to 39.1 ± 3.5% and fractional delivery of water at the early distal tubule from 26.4 ± 1.4 to 21.9 ± 1.0% (P &lt; 0.05 for each variable). Fractional delivery of Na+ at the early distal tubule did not change significantly.
3. Similar experiments were performed during partial aortic constriction to exclude the effects of increased perfusion pressure. The data obtained were similar, except that in this group the fractional delivery of Na+ at the early distal tubule decreased from 8.6 ± 0.7 to 6.8 ± 0.9% (P &lt; 0.05).
4. The relation between late proximal tubule Na+ delivery and Na+ reabsorption between late proximal and early distal tubule was not disturbed by angiotensin II. For water, however, this relation tended to shift to a higher reabsorption rate.
5. The decrease in fractional excretion of Li+ followed the decrease in proximal reabsorption as measured directly by micropuncture. Angiotensin II infusion did not appear to affect Li+ reabsorption beyond the proximal tubule. Distal fractional Na+ reabsorption estimated by the Li+ clearance increased significantly during angiotensin II infusion.
6. In conclusion, our data indicate that a Na+-retaining dose of angiotensin II increases Na+ reabsorption in the proximal tubule, an effect correctly indicated by the change in the fractional excretion of Li+, does not influence Na+ reabsorption in the loop of Henle beyond the proximal tubule, but may increase Na+ reabsorption in more distal segments.