bluuebunny/crossref_metadata_2025_split huggingface dataset:
Vascular and Hormonal Responses to Arginine: Provision of Substrate for Nitric Oxide or Non-Specific Effect?
Authors: MacAllister R. J. , Calver A. L. , Collier J. , Edwards C. M. B. , Herreros B. , Nussey S. S. , Vallance P. 
Published: August 2015

1. The vascular and hormonal effects of l- and d-arginine were compared in healthy subjects and in patients with insulin-dependent diabetes mellitus or untreated essential hypertension.
2. Infusion of l- or d-arginine (40 μmol/l) in the forearm vascular bed, sufficient to increase the local concentration approximately 20-fold, had no effect on blood flow or the vasodilator response to acetylcholine (30 and 100 nmol/min) in patients with insulin-dependent diabetes (n = 7) or essential hypertension (n = 7), or in age- and sex-matched control subjects (n = 7 in both groups).
3. Systemic infusion of 10 g of l-arginine (n = 5) or d-arginine (n = 3) increased plasma concentration of arginine approximately 20-fold without altering supine or erect haemodynamics. Increases in plasma insulin, prolactin and glucagon were seen with both enantiomers. The stereopurity of arginine was confirmed in a cell-culture assay system.
4. We conclude that, in healthy subjects and patients with essential hypertension or insulin-dependent diabetes, synthesis of nitric oxide within the vasculature is not limited by substrate availability. At high concentrations of arginine, non-stereospecific effects, including alterations in hormone concentration, occur. It remains to be determined whether these non-stereospecific hormonal changes might contribute to certain haemodynamic effects of arginine.
Aortic Distensibility in Patients with Cerebrovascular Disease
Authors: Lehmann E. D. , Hopkins K. D. , Jones R. L. , Rudd A. G. , Gosling R. G. 
Published: August 2015

1. Non-invasive aortic compliance measurements have been used previously to assess the distensibility of the aorta in several pathological conditions associated with increased cardiovascular risk. We set out to establish whether aortic compliance is abnormal in patients with stroke.
2. Pulse wave velocity measurements of thoracoabdominal aortic compliance were made in 20 stroke patients and 25 age- and sex-matched hospitalized, non-stroke control subjects putatively free of cardiovascular disease. Since compliance varies with non-chronic changes in blood pressure, a blood pressure corrected index of aortic distensibility, Cp, was calculated.
3. Aortic compliance was significantly reduced in patients with stroke compared with non-stroke control subjects (0.46 ± 0.27 versus 0.86 ± 0.34%/10 mmHg, P &lt; 0.0002), corresponding with higher values for pulse wave velocity. Stroke patients also had significantly higher systolic and diastolic blood pressures (P &lt; 0.02 and P &lt; 0.002 respectively) and total cholesterol levels (P &lt; 0.004) than the control subjects. Calculation of Cp did not alter the observation of stiffer aortas in the stroke cohort (P &lt; 0.0007).
4. In both stroke patient and control cohorts, as expected, inverse trends were observed between aortic compliance and blood pressure. Also as expected, in the control group Cp values did not show a relationship with blood pressure (r = 0.02, P = 0.092, not significant). However, in the stroke cohort a marked dependence of Cp on blood pressure was observed (r = −0.48, P = 0.03).
5. Transoesophageal echocardiographic studies have recently identified advanced atherosclerosis in the ascending aorta as a possible source of cerebral emboli and an independent risk factor for ischaemic stroke. Our observations of significantly stiffer thoracoabdominal aortas in patients with stroke lead us to hypothesize that a totally non-invasive assessment of aortic compliance may potentially prove a useful surrogate marker of such atherosclerotic risk.
6. Blood pressure-corrected indices of arterial elastic properties based on normotensive models are widely applied in the literature. Our observation that these indices exhibit a considerable blood pressure dependence leads us to urge caution in the use of such corrections, especially in hypertensive patients.
Circulating Angiotensin-Converting Enzyme, Von Willebrand Factor Antigen and Thrombomodulin in Exertional Heat Stroke
Authors: Shieh Shang-Der , Shiang Jeng-Chuan , Lin Yuh-Feng , Shiao Wen-Yen , Wang Jia-Yi 
Published: August 2015

1. Military recruits frequently succumb to exertional heat stroke during intensive training. Since widespread endothelial injury is often associated with exertional heat stroke, the relationship between changes in three circulating endothelial cell markers (angiotensin-converting enzyme, von Willebrand factor antigen and thrombomodulin) and exertional heat stroke was studied.
2. Twelve recruits who had succumbed to exertional heat stroke during basic physical training (5000 m running) were included in the study. Another 10 age-matched healthy subjects who had gone through the same physical training regimen were selected as controls.
3. Blood was withdrawn on admission and on discharge for analyses of angiotensin-converting enzyme, von Willebrand factor antigen and thrombomodulin. Other physiological parameters and biochemical analyses reflecting renal and liver functions were also recorded.
4. Our results indicated that these subjects with exertional heat stroke exhibited impaired liver function as revealed by the significant elevation of both serum glutamic oxaloacetic transaminase (P &lt; 0.05) and serum glutamic pyruvic transaminase (P &lt; 0.05) as compared with normal healthy control subjects. Unfortunately, these values remained mostly somewhat elevated on discharge, although serum glutamic oxaloacetic transaminase was reduced dramatically. Indices of kidney functions, including creatinine clearance and uric acid and phosphorus secretion, were not significantly different from those observed in healthy controls.
5. Circulating angiotensin-converting enzyme activities in exertional heat stroke patients on admission were significantly lower than in normal subjects (10.68 ± 2.15 versus 21.21 ± 3.18 nmol hippuric acid min−1ml−1, P&lt;0.05). In contrast, von Willebrand factor antigen, thrombomodulin and plasma renin activity were significantly elevated compared with corresponding values in healthy subjects (P &lt; 0.001, 0.05 and 0.01 respectively). The values of these endothelial markers returned to normal on discharge.
6. These data suggest that the decrease in angiotensin-converting enzyme and increase in von Willebrand factor antigen and thrombomodulin associated with exertional heat stroke may reflect endothelial injuries. Since endothelial injuries may trigger haemostatic failure and/or disseminated intravascular coagulation, the monitoring of these values might be useful for the evaluation of endothelial status in patients suffering from exertional heat stroke.
Total Antioxidant Capacity and Lipid Peroxidation during Liver Transplantation
Authors: Galley Helen F. , Richardson Norma , Howdle Peter D. , Walker Barry E. , Webster Nigel R. 
Published: August 2015

1. We assessed plasma total antioxidant capacity using enhanced chemiluminescence and plasma lipid peroxides in eight patients undergoing orthotopic liver transplantation and 26 healthy control subjects.
2. The antioxidant capacity of plasma decreased significantly on reperfusion of the donor liver (P &lt; 0.05) during liver transplantation, although levels were not lower in patients than in control subjects.
3. Pre-reperfusion antioxidant capacity correlated negatively with the concentration of lipid peroxidation products appearing in the plasma by the end of the transplant (P &lt; 0.02), but did not correlate with vitamin A or E concentrations.
4. This study provides evidence of oxidant stress during liver transplantation, as shown by antioxidant utilization associated with increased lipid peroxidation.
Effect of the Somatostatin Analogue, Octreotide, on Exercise-Induced Hypotension in Human Subjects with Chronic Sympathetic Failure
Authors: Smith G. D. P. , Alam M. , Watson L. P. , Mathias C. J. 
Published: August 2015

1. In autonomic failure, supine exercise lowers blood pressure and worsens postural hypotension. The somatostatin analogue, octreotide, reduces postprandial and postural hypotension, but its effects on exercise-induced hypotension and on postural hypotension post-exercise are unknown.
2. Eighteen subjects with chronic sympathetic denervation were studied; 12 had pure autonomic failure and six had additional neurological features of the Shy—Drager syndrome. Haemodynamic, hormonal and biochemical changes were measured before, during and after incremental supine leg exercise on two occasions: on no treatment and after subcutaneous octreotide. Exercise was performed 120 min after octreotide in eight subjects and 60 min after octreotide in ten subjects.
3. Octreotide did not improve exercise-induced hypotension; the blood pressure fall was greater during exercise, but the blood pressure level was no different than without treatment. Heart rate, stroke distance, cardiac index and systemic vascular resistance were similar at rest and changed to the same degree with exercise on and off octreotide. After octreotide, resting levels of serum growth hormone, plasma noradrenaline, adrenaline and renin were unchanged, but glucose was higher and insulin was lower. There was no change in biochemical and hormone levels during exercise either off or on octreotide.
4. After octreotide, although the rate of blood pressure recovery was similar post-exercise, the levels of blood pressure were higher than in the non-treatment phase and postural hypotension was improved before and after exercise.
5. In conclusion, in primary autonomic failure, octreotide did not improve exercise-induced hypotension in the supine position, suggesting that octreotide-sensitive vasodilatory peptides do not contribute to the blood pressure fall. With octreotide, supine blood pressure levels were higher post-exercise and postural hypotension was improved both before and after exercise.
Effect of Breathing, Pressure and Posture on Palatoglossal and Genioglossal Tone
Authors: Mathur Rajat , Mortimore Ian L. , Jan Mohammed A. , Douglas Neil J. 
Published: August 2015

1. Patency of the upper airway is critical to respiration. Although about half of patients with the sleep apnoea/hypopnoea syndrome obstruct their upper airway at the retropalatal level, the respiratory actions of the palatal muscles have been little studied. We have therefore tested the hypothesis that the nasopharyngeal dilator muscle palatoglossus is activated during inspiration and by negative pressure.
2. Using intramuscular wire electrodes inserted perorally, we have compared the response of palatoglossus and genioglossus to breathing, posture change and airway negative pressure in 10 normal awake subjects before and after topical anaesthesia. The results are expressed as a percentage of maximal electromyogram. Data were analysed by repeated-measures analysis of variance.
3. Inspiratory activity was exhibited by both genioglossus [inspiratory, 10% ± 2% (SEM); expiratory, 6% ± 1%, P = 0.001] and palatoglossus (inspiratory, 16% ± 5%, expiratory, 10% ± 3%, P = 0.016), but only genioglossus exhibited increased activity on lying (supine 10% ± 2%, erect 6% ± 1% maximum, P = 0.01).
4. One hundred milliseconds after negative pressure application, activity increased in both genioglossus (7% ± 2% and 13% ± 3% respectively, P = 0.02) and palatoglossus (8% ± 2% and 23% ± 6% respectively, P &lt; 0.001). After lignocaine surface anaesthesia to the nose and pharynx both genioglossus and palatoglossus still increased their activity in response to negative upper airway pressure, the extent of the increase being decreased for palatoglossus (P = 0.02) but not for genioglossus.
5. Thus, palatoglossus has respiratory activity and is activated by negative upper airway pressure.
Atrial Natriuretic Factor and Angiotensin Ii Stimulate Nitric Oxide Release from Human Proximal Tubular Cells
Authors: McLay J. S. , Chatterjee P. K. , Mistry S. K. , Weerakody R. P. , Jardine A. G. , McKay N. G. , Hawksworth G. M. 
Published: August 2015

1. It has been recently reported that angiotensin II can enhance atrial natriuretic factor-stimulated cyclic GMP release from brain capillary endothelial cells and stimulate directly the release of cyclic GMP by Neuro 2a cells. A possible mechanism mediating such cyclic GMP release could be via the production of nitric oxide and the resultant stimulation of soluble guanylate cyclase.
2. The ability of angiotensin II, atrial natriuretic factor and c(4–23) atrial natriuretic factor to stimulate nitric oxide production was investigated in primary cultures of human proximal tubular cells.
3. Freshly prepared human proximal tubular cells were seeded onto 6-well plates and allowed to reach confluence. Cells were then incubated with incremental concentrations of either angiotensin II, atrial natriuretic factor or c(4–23) atrial natriuretic factor alone for 1, 4, 12 or 24 h or in the presence of the nitric oxide synthase inhibitor NG-monomethyl-l-arginine. Angiotensin II was also incubated with human proximal tubular cells in the presence of the AT, and AT2 receptor antagonists DuP 753 and PD 123319.
4. Incubation of human proximal tubular cells with angiotensin II, atrial natriuretic factor or c(4–23) atrial natriuretic factor produced a dose- and time-dependent increase in nitric oxide production, which was inhibited in the presence of NG-monomethyl-l-arginine. A similar increase in nitric oxide production was observed after incubation with atrial natriuretic factor or c(4–23) atrial natriuretic factor.
5. The angiotensin-induced increase in nitric oxide production was not inhibited in the presence of either the angiotensin AT1 or AT2 receptor antagonists DuP 753 or PD 123319.
6. This study demonstrates that primary cultures of human proximal tubular cells can be stimulated to produce nitric oxide by both atrial natriuretic factor and angiotensin II. Furthermore, the atrial natriuretic factor-induced response appears to be mediated via the atrial natriuretic factor-C receptor, while the angiotensin II-induced response appears to be mediated by a novel, as yet unidentified, angiotensin II receptor.
Acute Effects of Central Neuropeptide Y Injection on Glucose Metabolism in Fasted Rats
Authors: Wilding J. P. H. , Kruszynska Y. T. , Lambert P. D. , Bloom S. R. 
Published: August 2015

1. Neuropeptide Y is a potent appetite stimulant and has been found to modulate glucose metabolism when given chronically. The acute effects of neuropeptide on peripheral glucose handling have not been studied in detail. We have studied the acute effects of central nervous system injection of neuropeptide on glucose metabolism in vivo in the rat.
2. Rats implanted with chronic cannulae in the third cerebral ventricle were injected with either neuropeptide Y or saline and peripheral insulin sensitivity was assessed during a hyperinsulinaemic euglycaemic clamp. The effect of centrally injected neuropeptide Y on post-absorptive glucose metabolism was studied using a constant infusion of [6-3H]glucose.
3. Infusion of neuropeptide Y resulted in a 18% increase in glucose requirement during the clamp, suggesting increased peripheral tissue responsiveness to insulin. Neuropeptide Y injection in 10 h fasted rats increased plasma glucose (area under curve 9.9 ± 0.2 versus 9.1 ± 0.1 mmol h−1 I−1, P &lt; 0.01), insulin (103 ± 23 versus 33 ± 8 pmol/l, P &lt; 0.01, at 30 min) and glucagon (5.5 ± 0.5 versus 3.1 ± 0.3 pmol/l, P &lt; 0.05, at 30 min). The increase in plasma glucose was due to an initial increase in the rate of appearance, which peaked between 20 and 30 min after neuropeptide Y infusion; over the entire 90 min 16% more glucose entered the systemic circulation in the neuropeptide Y-treated rats than in control rats, and the total quantity of glucose removed was also greater.
4. Neuropeptide Y in the central nervous system influences glucose metabolism by altering secretion of islet hormones, hepatic glucose production and the peripheral response to insulin.
Relationship between Serum Tryptophan and Tryptophan Metabolite Levels after Tryptophan Ingestion in Normal Subjects and Age-Related Cataract Patients
Authors: Truscott Roger J. W. , Elderfield Anthony J. 
Published: August 2015

1. Cataract is the single major cause of blindness worldwide; however, the reasons for the development of this condition remain unknown. It has been suggested that the essential amino acid tryptophan may be implicated in the aetiology but definitive evidence has been lacking.
2. The serum levels of tryptophan and seven of its metabolites have been measured in both cataract patients and control subjects, after administration of tryptophan, in order to determine the typical response profile and to discover whether differences could be found in tryptophan metabolism in the two groups.
3. Tryptophan, kynurenine, kynurenic acid, xanthurenic acid, 3-hydroxyanthranilic acid, 5-hydroxyanthranilic acid, 5-hydroxytryptophan and anthranilic acid were measured by HPLC with dual electrochemical and programmable wavelength fluorescence detection. Fasting cataract patients (n = 42) and control subjects (n = 37) were given an oral dose of l-tryptophan and sera were sampled at 0, 1, 2, 4 and 6 h.
4. Statistically significant differences in the distribution of data between the two groups were observed. The responses of kynurenine and 5-hydroxyanthranilic acid were higher in cataract patients, but those of kynurenic acid and total tryptophan were lower than in control subjects. No statistically significant differences in free tryptophan, anthranilic acid, 3-hydroxyanthranilic acid, xanthurenic acid or 5-hydroxytryptophan levels were noted.
5. We conclude that there is a major subgroup of age-related cataract patients with a dysfunction in the metabolism of tryptophan. This may be related to the onset of cataract. The mechanism remains to be established but may operate via the action of tryptophan metabolites, such as 5-hydroxyanthranilic acid, which become reactive towards protein upon oxidation.
The Cost of Breathing in Stable Chronic Obstructive Pulmonary Disease
Authors: Hugli Olivier , Schutz Yves , Fitting Jean-William 
Published: August 2015

1. The hypermetabolism frequently observed at rest in patients with chronic obstructive pulmonary disease has been attributed to a high cost of breathing. However, measurement of the cost of breathing by the usual hyperventilation procedure is fraught with methodological problems. The purpose of this study was to measure more directly the cost of breathing in a group of ambulatory patients with stable chronic obstructive pulmonary disease.
2. The cost of breathing was calculated as the difference in oxygen consumption measured by indirect calorimetry between spontaneous breathing and noninvasive mechanical ventilation. Inspiratory muscle rest was achieved by negative or positive pressure ventilation and assessed by the recording of surface electromyograms of the diaphragm and parasternal intercostal muscles.
3. Seven tests were performed in six ambulatory patients with stable chronic obstructive pulmonary disease, four tests using positive pressure ventilation and three with negative pressure ventilation. During mechanical ventilation, the electromyographic activity of the diaphragm decreased by 70 ± 22%, while that of the parasternals was suppressed in four tests, and remained unchanged in three. However, oxygen consumption was only 1.6 ± 6.2% lower during mechanical ventilation.
4. The cost of breathing measured in this study was therefore much lower than previously published values. Stress was not likely to influence the results, as both the heart rate and plasma catecholamines did not change between spontaneous breathing and mechanical ventilation. These results suggest that the cost of breathing in ambulatory patients with stable chronic obstructive pulmonary disease may be lower than previously estimated.
Expression of Endothelin Peptides and Mrna in the Human Heart
Authors: Plumpton C. , Ashby M. J. , Kuc R. E. , O'Reilly G. , Davenport A. P. 
Published: August 2015

1. We have examined the expression of endothelin isoforms and their precursors in the human heart using RIA, HPLC, immunocytochemistry and reverse transcriptase—polymerase chain reaction assays.
2. Highly specific RIAs were used to measure the levels of mature endothelin and big endothelin-1 immunoreactivity in extracts of human right ventricle. There was no significant difference between samples from patients with ischaemic heart disease and idiopathic dilated cardiomyopathy.
3. HPLC coupled with RIAs allowed the separation and identification of the three mature isoforms of endothelin, big endothelin-1 and the C-terminal fragment of big endothelin-1. In extracts of human endocardial endothelial cells, peaks of immunoreactivity that co-eluted with authentic endothelin-1, big endothelin-1 and C-terminal fragment were found.
4. Intense immunocytochemical staining of mature endothelin immunoreactivity was detected in the cytoplasm of endothelial cells of all regions of the heart tested. Big endothelin-1 immunoreactivity mirrored that of the mature peptide and, in two of three individuals tested, big endothelin-2 immunoreactivity was also detected. No big endothelin-3 immunoreactivity was detected in any of the tissues examined.
5. Reverse transcriptase—polymerase chain reaction assays demonstrated endothelin-1 and endothelin-2 mRNA in all three samples of human left ventricle tested. In two of the individuals, additional bands were also detected with the endothelin-2 primers which corresponded to splice variants. There was no evidence for the expression of endothelin-3 mRNA.
6. These data suggest that endothelin-1 is the predominant isoform of endothelin in the human heart and is probably largely synthesized by the endothelial cells within the heart. If released from the endothelial cells in vivo, this potent cardiotonic peptide may play an important paracrine role in human cardiovascular function.