bluuebunny/crossref_metadata_2025_split huggingface dataset:
Regulation of cAMP in a lymphocyte preparation isolated from peripheral venous blood in human subjects: the significance of residual thrombocytes, noradrenaline and prostaglandins
Authors: SØNDERGAARD Susanne B. , KNUDSEN Jens H. , CHRISTENSEN Niels J. 
Published: August 2015

1.The aim of the study was to elucidate the mechanism of the previously reported close correlation observed between noradrenaline and cAMP in a lymphocyte preparation (LP) isolated from peripheral venous blood in healthy subjects. A close correlation was also obtained in the present study between lymphocyte noradrenaline and adrenaline and cAMP both in the basal state and after stimulation with isoproterenol (P< 0.05 to 0.007).
2.Although 99% of the thrombocytes were removed from the LP during the washing procedure, LP contained approximately one thrombocyte per lymphocyte. The noradrenaline concentration in LP which could be ascribed to residual thrombocytes, calculated from the average noradrenaline concentration in thrombocytes and the number of thrombocytes in LP, correlated closely to noradrenaline in LP (P< 0.007).
3.To test the hypothesis that noradrenaline in LP was primarily derived from plasma, we studied three patients with phaeochromocytoma, who had high levels of noradrenaline and adrenaline both in plasma and in LP.
4.Further studies showed that the addition of thrombocytes to LP increased cAMP. The response was inhibited by indomethacin, whereas the addition of cimetidine and propranolol had no effect on basal or thrombocyte-stimulated cAMP.
5.We conclude that noradrenaline in LP is a marker of the number of residual thrombocytes. The addition of thrombocytes to LP increased cAMP in lymphocytes. This response was not mediated by catecholamines but possibly by prostaglandins.
Isolation and characterization of the viscous, high-molecular-mass microbial carbohydrate fraction from faeces of healthy subjects and patients with Crohn's disease and the consequences for a therapeutic approach
Authors: RUSELER-VAN EMBDEN Johanneke G. H. , VAN LIESHOUT Leo M. C. , BINNEMA Doede J. , HAZENBERG Maarten P. 
Published: August 2015

1.An earlier study by our group revealed that the viscosity of faeces from patients with Crohn's disease is significantly lower than that of healthy subjects. This is due to low concentrations of a high-molecular-mass carbohydrate, probably of bacterial origin. The cause of this phenomenon might be the impaired barrier function of the gut mucosa. Low viscosity may allow close contact of intestinal contents (bacterial products and toxins) with the intestinal wall. This could play a role in the maintenance of the disease.
2.The first aim of this study was to investigate the high-molecular-mass carbohydrate fraction, responsible for viscosity, in detail. We also tried (in a pilot study) to raise the intestinal viscosity of patients with Crohn's disease with the undegradable food additive hydroxypropylcellulose (E463), in an attempt to alleviate clinical symptoms.
3.The high-molecular-mass fraction (&gt; 300 ;kDa) responsible for faecal viscosity was sensitive to lysozyme and contained high levels of muramic acid. It was concluded that this material consisted mainly of peptidoglycan polysaccharides and was consequently of bacterial origin. The muramic acid in material from patients with Crohn's disease was 7.5 (1.5–13.9)%, which was less than in healthy subjects [11.4 (8.5–24.1)%; P = 0.0004]. Furthermore, viscosity in material from patients with Crohn's disease was found to be half [14.9 (1.0–33.6) cP] of that found in healthy subjects [35.0 (2.7–90.7) cP; P = 0.004].
4.A daily dose of 1 ;g of hydroxypropylcellulose caused an increase in faecal viscosity in patients with Crohn's disease (from 1.4 to 2.3 cP) and in healthy subjects (from 4.9 to 7.5 cP). Faecal consistency improved in patients with Crohn's disease (from watery and loose to formed) and the defecation frequency decreased from 3–4 to about 2 times a day. No changes in defecation patterns were found in healthy subjects.
5.These data indicate that the high-molecular-mass fraction that is responsible for faecal viscosity is peptidoglycan. Furthermore, a daily dose of a hydroxypropylcellulose solution to increase the viscosity of the intestinal contents of patients with Crohn's disease might be beneficial. This approach merits further study.
Effect of sodium nitroprusside and L-arginine methyl ester on rat hearts stored at 4 °C for 24 h
Authors: FAGBEMI Oluwole S. , NORTHOVER Basil J. 
Published: August 2015

1.This study examined the effects of altering nitric oxide levels with sodium nitroprusside or l-arginine in rat hearts stored hypothermically.
2.Hearts were microperfused at 4 ;°C for 24 ;h with a modified Krebs–Henseleit buffer (KHB) that contained either sodium nitroprusside, l-arginine, l-arginine methyl ester or dexamethasone.
3.After hypothermic storage, hearts were rewarmed to 37 ;°C with KHB alone or KHB containing sodium nitroprusside or l-arginine. Cardiac function was then assessed in either Langendorff mode or working heart mode.
4.Compared with values from fresh unstored hearts, hypothermic stored hearts showed a significant decrease in coronary flow and left ventricular developed pressure when the stored hearts were perfused in Langendorff mode. These hearts also produced less aortic flow and cardiac output when perfused in the working mode.
5.Hearts hypothermically microperfused with buffer containing either l-arginine or sodium nitroprusside and then reperfused in the Langendorff mode with untreated KHB buffer had the highest left ventricular developed pressure and coronary flow values. Aortic flow and cardiac output were also higher in these hearts.
6.In all groups of stored hearts, the concentrations of both ATP and creatine phosphate were significantly low, when compared with values from freshly isolated hearts. Addition of dexamethasone to the buffer either during storage or during reperfusion had no beneficial effect on high-energy phosphate loss or cardiac performance of stored hearts.
7.This study showed that the addition of nitric oxide donors to storage buffer significantly improves cardiac function on normothermic reperfusion. The improved functional recovery is unrelated to the high-energy phosphate content of these hearts.
Reproducibility of three different methods of measuring baroreflex sensitivity in normal subjects
Authors: LORD S. W. , CLAYTON R. H. , HALL M. C. S. , GRAY J. C. , MURRAY A. , McCOMB J. M. , KENNY R. A. 
Published: August 2015

1.Baroreflex sensitivity is a useful tool for investigating cardiovascular reflexes in a number of clinical settings. Several different methods of measuring baroreflex sensitivity are available. In order to determine a clinically useful non-invasive method of measuring baroreflex sensitivity we compared two methods (spectral analysis and the Valsalva manoeuvre) with regard to reproducibility, agreement with a standard invasive method (phenylephrine infusion) and failure rate.
2.Twenty-six healthy subjects aged 22 to 63 years attended on three separate occasions for measurement of baroreflex sensitivity using the different methods. The effect of a recent head-up tilt on baroreflex sensitivity was measured.
3.Reproducibility was best for the low-frequency component of the spectral method [coefficient of variation 25.0% (range 3.5–42.4%)] and worst for the Valsalva method [coefficient of variation 29.3% (range 13.8–93.1%)]. Both non-invasive methods overestimated values compared with the phenylephrine method [bias of low-frequency component of the spectral method, 1.17 (0.38–3.6); bias of the Valsalva method, 1.13 (0.19–6.7)]. The high-frequency component of the spectral method did not agree with the phenylephrine method.
4.The spectral analysis method had the fewest failures (seven subjects with a failure on at least one occasion), and the phenylephrine method the most (16 subjects with a failure on at least one occasion). A short head-up tilt did not affect the subsequent non-invasive measurement of baroreflex sensitivity.
5.It was concluded that the low-frequency component of the spectral method was the most clinically useful non-invasive measurement of baroreflex sensitivity.
Aldosterone blunts the baroreflex response in man
Authors: YEE K. M. , STRUTHERS A. D. 
Published: August 2015

1. Recent animal evidence suggests that aldosterone, like angiotensin II, may possess detrimental autonomic modulating properties. Aldosterone has been shown to impair the baroreflex response in animal models. This study is designed to test the hypothesis that aldosterone directly attenuates the baroreflex in vivo in man.
2. Fourteen healthy male volunteers [mean age (S.D.) 25 (9) years] received intravenous d-aldosterone (12 pmol·min-1·kg-1) and 5% dextrose (vehicle) in a double-blind crossover fashion, co-infused with incremental doses of intravenous phenylephrine and sodium nitroprusside. Aldosterone had no significant effect on resting blood pressure, heart rate or baroreflex response to sodium nitroprusside. However, reflex responses to phenylephrine were impaired with aldosterone (P&lt; 0.01) while blood pressure responses were unaltered. Baroreflex sensitivity was significantly blunted in the aldosterone group [8.36±2.19 versus 10.12±2.27 ms/mmHg; P&lt; 0.04].
3. This study confirms previous observations from animal models that aldosterone impairs the baroreflex response. High aldosterone levels may contribute to the baroreflex dysfunction in cardiovascular diseases such as hypertension and heart failure.
Subcutaneous glucagon-like peptide-1 (7-36) amide is insulinotropic and can cause hypoglycaemia in fasted healthy subjects
Authors: EDWARDS C. Mark B. , TODD Jeannie F. , GHATEI Mohammad A. , BLOOM Stephen R. 
Published: August 2015

1. Glucagon-like peptide-1 (7-36) amide (GLP-1) is a gut hormone released postprandially that stimulates insulin secretion, suppresses glucagon secretion and delays gastric emptying. The insulinotropic action of GLP-1 is more potent under hyperglycaemic conditions. Several published studies have indicated the therapeutic potential of subcutaneous GLP-1 in non-insulin-dependent (Type 2) diabetes mellitus.
2. We investigated whether subcutaneous GLP-1, at a dose shown to improve glycaemic control in early Type 2 diabetes, is insulinotropic at normal fasting glucose concentrations. A double-blind, randomized, crossover study of 10 healthy subjects injected with GLP-1 or saline subcutaneously after a 16 h fast was performed. The effect on cardiovascular parameters was also examined.
3. GLP-1 caused a near 5-fold rise in plasma insulin concentration. After treatment with GLP-1, circulating plasma glucose concentrations fell below the normal range in all subjects. One subject had symptoms of hypoglycaemia after GLP-1. A rise in pulse rate was found which correlated with the fall in plasma glucose concentration. An increase in blood pressure occurred with GLP-1 injection which was seen at the same time as the rise in plasma GLP-1 concentrations.
4. This study indicates that subcutaneous GLP-1 can override the normal homoeostatic mechanism maintaining fasting plasma glucose in man, and is also associated with an increase in blood pressure.
Effects of ursodeoxycholic acid on systemic, renal and forearm haemodynamics and sodium homoeostasis in cirrhotic patients with refractory ascites
Authors: WONG Florence , BOMZON Arieh , ALLARD Johane , LIU Peter , BLENDIS Laurence 
Published: August 2015

Systemic arterial vasodilatation has been implicated in the pathogenesis of sodium retention in cirrhosis. Hydrophobic bile acids, which have vasodilatory actions, may be involved. Ursodeoxycholic acid, a hydrophilic bile acid, could potentially decrease systemic arterial vasodilatation, possibly due to its antioxidant effects, and improve sodium handling in cirrhosis. The effects of ursodeoxycholic acid on systemic, renal and forearm haemodynamics, liver function and renal sodium handling were assessed in vasodilated cirrhotic patients with refractory ascites treated with a transjugular intrahepatic porto-systemic shunt (TIPS). Eight cirrhotic patients with refractory ascites without TIPS placement served as controls for the sodium handling effects of ursodeoxycholic acid. From 1 month post TIPS, seven patients were studied before, after 1 month of treatment with ursodeoxycholic acid (15 mg·day-1·kg-1) and at 1 month follow-up. Lipid peroxidation products were used as indices of its antioxidant effects. Ursodeoxycholic acid caused a significant reduction in sodium excretion in both groups (P< 0.05). This, in the post-TIPS patients (urinary sodium excretion: 35±8 mmol/day at 1 month versus 93±21 mmol/day at baseline, P< 0.05), was due to a significant increase in sodium reabsorption proximal to the distal tubule (P< 0.05), without any significant changes in systemic, renal or forearm haemodynamics, or in liver function. No significant change in lipid peroxidation products was observed. We conclude that: (i) in cirrhotic patients with refractory ascites, ursodeoxycholic acid causes sodium retention, (ii) the abnormality in sodium handling in the post-TIPS cirrhotic patients appears to be the result of a direct effect on the proximal nephron, suggesting that factors other than systemic vasodilatation also contribute to sodium retention in cirrhosis, (iii) caution should be exercised in administering ursodeoxycholic acid in cirrhotic patients with ascites.
Acute effect of ephedrine on 24-h energy balance
Authors: SHANNON John R. , GOTTESDIENER Keith , JORDAN Jens , CHEN Kong , FLATTERY Stacey , LARSON Patrick J. , CANDELORE Mari Rios , GERTZ Barry , ROBERTSON David , SUN Ming 
Published: August 2015

Ephedrine is used to help achieve weight control. Data on its true efficacy and mechanisms in altering energy balance in human subjects are limited. We aimed to determine the acute effect of ephedrine on 24-h energy expenditure, mechanical work and urinary catecholamines in a double-blind, randomized, placebo-controlled, two-period crossover study. Ten healthy volunteers were given ephedrine (50 mg) or placebo thrice daily during each of two 24-h periods (ephedrine and placebo) in a whole-room indirect calorimeter, which accurately measures minute-by-minute energy expenditure and mechanical work. Measurements were taken of 24-h energy expenditure, mechanical work, urinary catecholamines and binding of (±)ephedrine in vitro to human β1-, β2- and β3-adrenoreceptors. Twenty-four-hour energy expenditure was 3.6% greater (8965±1301 versus 8648±1347 kJ, P< 0.05) with ephedrine than with placebo, but mechanical work was not different between the ephedrine and placebo periods. Noradrenaline excretion was lower with ephedrine (0.032±0.011 μg/mg creatinine) compared with placebo (0.044±0.012 μg/mg creatinine) (P< 0.05). (±)Ephedrine is a relatively weak partial agonist of human β1- and β2-adrenoreceptors, and had no detectable activity at human β3-adrenoreceptors. Ephedrine (50 mg thrice daily) modestly increases energy expenditure in normal human subjects. A lack of binding of ephedrine to β3-adrenoreceptors and the observed decrease in urinary noradrenaline during ephedrine treatment suggest that the thermogenic effect of ephedrine results from direct β1-/β2-adrenoreceptor agonism. An indirect β3-adrenergic effect through the release of noradrenaline seems unlikely as urinary noradrenaline decreased significantly with ephedrine.
Uptake and antioxidant effects of ergothioneine in human erythrocytes
Authors: MITSUYAMA Hiroki , MAY James M. 
Published: August 2015

Ergothioneine is a fungal metabolite that may have antioxidant functions in mammalian cells. Although it accumulates to low millimolar concentrations in liver and other tissues, it is not thought to be taken up by mature erythrocytes. During a study of the function of ergothioneine as an antioxidant in human erythrocytes, we found that these cells do take up ergothioneine from the surrounding medium. Ergothioneine concentrations in freshly prepared erythrocytes were 2–9-fold higher than in plasma from the same donor. Slow but progressive accumulation of ergothioneine to about 125% of basal levels was observed in erythrocytes over a 4 h incubation. After a 2 h incubation, intracellular ergothioneine concentrations rose on addition of increasing amounts of ergothioneine to the incubation medium, although saturation was not evident in cells from all donors. Both initial levels and rates of ergothioneine uptake varied in erythrocytes from different donors. Intracellular ergothioneine was stable to depletion of GSH by N-ethylmaleimide and to a more severe oxidant stress induced by hydrogen peroxide in the presence of catalase. These results show that human erythrocytes do take up ergothioneine; however, the GSH results do not support an antioxidant role for ergothioneine in erythrocytes.
Increased intracellular calcium and decreased activities of leucocyte Na+,K+-ATPase and Ca2+-ATPase in asthma
Authors: CHHABRA Sunil Kumar , KHANDUJA Anita , JAIN Deepika 
Published: August 2015

The present study was carried out to determine the intracellular free calcium concentration ([Ca2+]i) and the activity of its regulatory enzymes (Na+,K+-ATPase and Ca2+-ATPase) in leucocytes. Levels of plasma lysophosphatidylcholine (LPC) were also measured. Then the relationship between these parameters and the clinical severity of asthma and bronchial reactivity was studied. Patients with asthma were divided into three groups: acute asthma (subjects in acute exacerbation), uncontrolled asthma (subjects currently symptomatic) and stable asthma (subjects currently asymptomatic). A group of normal subjects was also studied. Spirometry, specific airway conductance and bronchial reactivity measurements were carried out. The following biochemical parameters were studied in venous blood: leucocyte [Ca2+]i, Na+,K+-ATPase and Ca2+-ATPase activities, and plasma LPC. Leucocyte [Ca2+]i was increased and the activities of Na+,K+-ATPase and Ca2+-ATPase were decreased in patients with asthma. Plasma levels of LPC were also increased. These changes were observed to be greatest among asthmatics in acute exacerbation of asthma, and lesser in magnitude in patients with less severe asthma. The activities of both ATPases were found to have a significant positive correlation, and [Ca2+]i and the levels of plasma LPC a significant negative correlation, with predicted forced expiratory volume in 1 s (FEV1). No significant correlation was observed between the biochemical parameters and bronchial reactivity. It is concluded that intracellular calcium homoeostasis is abnormal in asthma; specifically, the activities of Na+,K+-ATPase and Ca2+-ATPase are decreased. These abnormalities may modulate the clinical severity of asthma.
Comparable vasorelaxant effects of 17α- and 17β-oestradiol on rat mesenteric resistance arteries: an action independent of the oestrogen receptor
Authors: NADERALI Ebrahim K. , WALKER Adrian B. , DOYLE Patrick , WILLIAMS Gareth 
Published: August 2015

17β-Oestradiol (17βE2) has vasorelaxant properties that may contribute to its beneficial cardiovascular effects. The mechanism of vasorelaxation remains controversial, but does not appear to involve interaction of 17βE2 with its nuclear receptor. The present study examined the effects on resistance arteries of 17βE2 and its isomer, 17α-oestradiol (17αE2), which does not bind to the classical oestrogen receptor. In arteries precontracted with either noradrenaline or KCl, 17βE2 and 17αE2 caused comparable relaxation in a concentration-dependent manner over the concentration range 0.1–10 μmol/l, with no significant difference in the maximal effect obtained. Pre-incubation of the arteries with 17βE2 or 17αE2 for 15 min reduced the magnitude and duration of the force generated with both noradrenaline and KCl to a comparable degree. Vasorelaxation induced by either 17βE2 or 17αE2 was not blocked by an inhibitor of NO synthase or by protein synthesis inhibitors, indicating that vasodilatation is not dependent upon either NO generation or protein synthesis. In the absence of extracellular calcium, both oestradiols still relaxed arteries precontracted with NA, suggesting that they inhibit intracellular calcium release. Both 17βE2 and 17αE2 therefore have important and comparable vasorelaxant properties that do not require interaction with the nuclear oestrogen receptor. Direct interactions with the cell membrane or with ion-channel proteins may be responsible.
Effects of lipoproteins from pre-eclamptic women on umbilical endothelial cell 6-oxo-prostaglandin F1α and endothelin 1 synthesis, and nitric oxide synthase 3 mRNA expression
Authors: BARDEN A. , BEILIN L. J. , BOTH K. , RITCHIE J. , LEEDMAN P. , WALTERS B. N. , MICHAEL C. A. 
Published: August 2015

In order to evaluate whether lipid abnormalities may contribute to endothelial dysfunction in pre-eclampsia, the present study examined the in vitro effects of very-low-density lipoprotein (VLDL), low-density lipoprotein (LDL) and high-density lipoprotein (HDL), isolated from women with pre-eclampsia and matched controls, on the endothelial synthesis of 6-oxo-prostaglandin F1α (6-oxo-PGF1α; a metabolite of prostacyclin) and endothelin 1, and on the expression of nitric oxide synthase 3 (NOS3) mRNA. VLDL, LDL and HDL cholesterol were isolated from 20 pre-eclamptic and 20 age- and gestation-matched normal pregnant women. The lipoproteins (50 μg/ml) and lipoprotein-free control plasma were incubated for 1, 3 and 6 h at 37 °C with a human umbilical endothelial cell line. The synthesis of 6-oxo-PGF1α and endothelin 1, and NOS3 mRNA expression, were measured at each time point. VLDL from pre-eclamptic women stimulated endothelial cell 6-oxo-PGF1α synthesis to a lesser extent than that from normal pregnant women (P< 0.05). LDL from women with pre-eclampsia also stimulated 6-oxo-PGF1α synthesis to a lesser extent than LDL from normal pregnant women, but the effect was less sustained. The effect of HDL from women with pre-eclampsia on 6-oxo-PGF1α synthesis was similar to that of HDL from normal pregnant women. The pre-incubation levels of lipid peroxides in VLDL and LDL were not different between the normal pregnant and pre-eclamptic women, and cannot account for the decrease in 6-oxo-PGF1α synthesis. VLDL, LDL and HDL from women with pre-eclampsia did not affect endothelial cell synthesis of endothelin 1 or expression of NOS3 mRNA differently from lipoproteins from normal pregnant women. This study suggests that VLDL, and to a lesser extent LDL, from women with pre-eclampsia could potentially contribute to the reduced systemic 6-oxo-PGF1α synthesis observed in the pre-eclamptic syndrome.