bluuebunny/crossref_metadata_2025_split huggingface dataset:
Plasma Leptin in Chronic Inflammatory Bowel Disease and HIV: Implications for the Pathogenesis of Anorexia and Weight Loss
Authors: Ballinger Anne , Kelly Paul , Hallyburton Elizabeth , Besser Rachel , Farthing Michael 
Published: August 2015

1. Leptin inhibits food intake and is an important regulator of long-term energy balance. In rodents, plasma concentrations of leptin are increased by administration of interleukin-1 and tumour necrosis factor. Hyperleptinaemia may mediate the anorexia and weight loss which is observed in chronic infections and inflammatory conditions.
2. Plasma leptin and soluble tumour necrosis factor receptor (sTNF-r55) concentrations were measured in patients with inflammatory bowel disease and acquired immunodeficiency syndrome (AIDS), and healthy controls.
3. The patients with AIDS were severely wasted [% body fat 12 (9–16); median (interquartile range)] compared with those with inflammatory bowel disease (25.1 (19–31.5)] and control subjects [29.4 (23.6–37.8)]. Leptin concentrations were highly correlated with percentage body fat in controls (r = 0.74, P &lt; 0.001) and patients with IBD (r = 0.73, P &lt; 0.001) but not in the patients with AIDS (r = −0.024). Leptin concentrations were similar in the inflammatory bowel disease (4.8 (2.6–10.1) ng/ml] and control groups [8.0 (3.1–14.1) ng/ml] but were significantly lower (P &lt; 0.05) in patients with AIDS (1.8 (1.5–2.3) ng/ml] after 23 patients were matched for sex and percentage body fat in patients with inflammatory bowel disease (2.4 (1.8–4.1) ng/ml]. Plasma concentrations of sTNF-r55 were higher in both the patients with inflammatory bowel disease [0.19 (0.16–0.23) ng/ml] and those with AIDS [4.8 (2.8–7.3) ng/ml] compared with controls [0.14 (0.09–0.16) ng/ml] but were not correlated with either percentage body fat or plasma leptin concentrations.
4. Hyperleptinaemia does not appear to mediate the anorexia and weight loss associated with inflammatory bowel disease and AIDS. In patients with AIDS with extreme wasting there was no relationship between body fat and leptin and this may be related to the rapid weight loss which occurs in these patients.
Abnormal Transoesophageal Doppler Coronary Flow Reserve in Patients with Dilated Cardiomyopathy: Relationship to Exercise Capacity
Authors: Chati Z. , Bruntz J. F. , Ethévenot G. , Aliot E. , Zannad F. 
Published: August 2015

1. In patients with dilated cardiomyopathy, abnormal myocardial blood flow may contribute to poor myocardial function.
2. The aim of this study was to investigate the possible contribution of abnormal myocardial blood flow to the limitation of exercise capacity in patients with dilated cardiomyopathy.
3. Coronary flow reserve was assessed in 16 patients with dilated cardiomyopathy and 9 matched normal control individuals. All participants had angiographically normal coronary arteries. At rest and after dipyridamole infusion (0.56 mg/kg intravenously), peak systolic and diastolic coronary flow velocities were measured in the proximal left anterior descending coronary artery using transoesophageal pulsed Doppler echocardiography, guided by colour flow imaging. Coronary flow reserve was calculated as the ratio of hyperaemic to basal diastolic and systolic peak coronary flow reserve.
4. Baseline diastolic and systolic coronary flow velocities were significantly higher in patients (50 ± 6 and 30 ± 4 cm/s respectively) compared with control individuals (37 ± 3 and 20 ± 1 cm/s respectively) (mean ± S.E.M.) (P &lt; 0.05). Diastolic and systolic peak coronary flow reserve were significantly lower in patients (1.60 ± 0.14 and 1.40 ± 0.09 respectively) compared with control individuals (2.89 ± 0.15 and 2.17 ± 0.17 respectively) (P &lt; 0.001). Although peak Vo2 and exercise time were significantly lower in patients compared with control individuals, coronary flow reserve did not correlate to exercise capacity in patients with dilated cardiomyopathy.
5. These results confirm the abnormalities of coronary flow reserve previously observed in patients with dilated cardiomyopathy, but suggest that such abnormalities do not contribute to the limitation of exercise capacity in these patients.
Regulation of Mitochondrial ATP Synthase Activity in Human Myocardium
Authors: Das Anibh M. 
Published: August 2015

1. In previous studies regulation of the F1F0-ATPase of mitochondrial complex V (ATP synthase) has been demonstrated in rat cardiomyocytes, canine mycocardium and skeletal muscle from children. The aim of the present study was to examine regulation of ATP synthase in human myocardium in response to different metabolic states.
2. Biopsy material was obtained from 10 children undergoing cardiac surgery. Mitochondria in the post-nuclear supernatant were incubated under different metabolic conditions for 15 min and then broken by sonication. ATP synthase was measured spectrophotometrically using a coupled enzyme assay.
3. ATP synthase can be rapidly measured in sonicated preparations of heart mitochondria from children. We show that direct regulation at the level of ATP synthase occurs in these mitochondria. ATP synthase capacity is decreased in response to blocking of the respiratory chain by cyanide (mimicking anoxia) or uncoupling of mitochondria, falling to 76% and 66% of control values respectively. Upregulation of ATP synthase can be demonstrated in heart mitochondria when the calcium concentration in the incubation medium is increased to 5 μM (130% of control).
4. ATP synthase is actively regulated in heart mitochondria from children. The enzyme is upregulated in response to increased calcium. This transition may reflect the increased energy demand when cardiac workload is increased.
Renoprotective Differences between Perindopril and Enalapril in the Diabetic Hypertensive Rat Do Not Reflect Glomerular Angiotensin-Converting Enzyme Activity
Authors: Duggan K. A. , Hodge G. , Makarious M. M. , Charlesworth J. A. 
Published: August 2015

1. The various angiotensin-converting enzyme inhibitors have structural differences which affect their affinities for the catalytic sites on converting enzyme. We postulated that such differences might result in differences in renoprotective efficacy. We investigated this in the diabetic spontaneous hypertensive rat. We also investigated whether these differences might reflect variations in glomerular or plasma angiotensin-converting enzyme activity.
2. One week after induction of diabetes, rats were started on antihypertensive therapy: enalapril, 10 mg · day−1 · kg−1, or perindopril, 4 mg · day−1 · kg−1, in the drinking water. After 3 months, the rats were killed, blood samples were taken and tissues were harvested. Angiotensin-converting enzyme activity in isolated glomeruli and plasma was measured by fluorimetric assay. Glomerular protein content was also determined.
3. Urinary protein excretion was significantly lower in perindopril-treated rats than in either controls (P &lt; 0.0005) or enalapril-treated rats P &lt; 0.05). Glomerular protein content was also lower in perindopril-treated rats (P &lt; 0.05 versus enalapril; P &lt; 0.005 versus control). There was no difference in glomerular angiotensin-converting enzyme activity between the two inhibitors although both were lower than control values (enalapril P &lt; 0.025; perindopril P &lt; 0.025). Plasma angiotensin-converting enzyme activity was significantly lower in the perindopril group than in either control (P &lt; 0.005) or the enalapril group (P &lt; 0.01).
4. We conclude that in the spontaneous hypertensive rat with streptozotocin-induced diabetes, perindopril is more effective than enalapril in reducing proteinuria and glomerular protein accumulation. This difference does not result from differences in glomerular-converting enzyme activity.
Effects of Skin Cooling on Airway Reactivity in Asthma
Authors: Skowronski M. E. , Ciufo R. , Nelson J. A. , McFadden E. R. 
Published: August 2015

1. Environmental contact with cold air is a common cause of respiratory distress in obstructive lung disease, and direct and reflex changes in bronchial calibre are well documented with this stimulus when it is inhaled or contacts the exposed skin respectively. It is now known that skin chilling does not amplify the effects of breathing cold air, but it is not established if this lack of interaction is unique, or applies to other forms of airway constrictors.
2. To provide data on this issue, 10 subjects with atopic asthma underwent methacholine bronchoprovocations with and without chilling of the integument of their heads and thoraces for 30 min. Chilling was accomplished with a specially designed thermal garment. Spirometry as well as core and skin temperatures were serially monitored during all experiments.
3. In the control phase (no cooling), integumental temperatures rose slightly, the forced expiratory volume in 1.0 s (FEV1.0) did not change, and the mean provocative concentration of methacholine required to reduce the FEV1.0 by 20% (PC20 meth) was 0.47 ± 0.17 mg/ml (2.4 ± 0.87 mmol/l). In the cold trial, the temperature of the back fell 5.1 ± 1.7 °C to 28.7 ± 1.8 °C (P &lt; 0.01), core temperatures did not change, and airway obstruction developed (ΔFEV1.0 = −6.7 ± 2.1%; P &lt; 0.05). The PC20 meth, however, was unaltered [PC20 meth = 0.45 ± 0.13 mg/ml (2.3 ± 0.66 mmol/1); P = 0.85].
4. These results demonstrate that although skin cooling produces mild airway obstruction in subjects with asthma, it does not change the response to non-specific bronchoconstrictors such as methacholine.
Cardiovascular Autonomic Testing in Adolescents with Type I (Insulin-Dependent) Diabetes Mellitus: An 18-Month Follow-up Study
Authors: Scaramuzza Andrea , Salvucci Fabrizio , Leuzzi Stefano , Radaelli Alberto , d'Annunzio Giuseppe , Fratino Pietro , Lorini Renata , Bernardi Luciano 
Published: August 2015

1. Autonomic abnormalities are frequent in adult patients with diabetes mellitus and progress slowly; little is known about frequency and progression of autonomic abnormalities in childhood.
2. To assess whether autonomic abnormalities are already present in childhood, we evaluated the cardiovascular reflexes, the spectral analysis of spontaneous fluctuations in RR interval and blood pressure (low- and high-frequency), and the baroreflex sensitivity at rest, and after vagal (controlled breathing) and sympathetic activation (tilting) in 25 adolescents with Type I diabetes mellitus, aged 10–17 years, at baseline and after 18 months follow-up, and in 20 age- and sex-matched controls.
3. Cardiovascular reflexes were similar in both patients and controls. Similar significant changes in percentage low- and high-frequency (P &lt; 0.005) from rest to tilting and to control breathing were observed in both patients and controls. The baroreflex sensitivity was also similar in patients and controls. Mild and non-systematic correlations were observed between autonomic tests and disease duration or metabolic control. After 18 months follow-up no changes were observed in any of the measured variables. Correlations with metabolic control remained unchanged.
4. These results indicate a substantial stability of cardiovascular autonomic function in childhood diabetes, and suggest that autonomic abnormalities are likely to develop at an older age.
Effects of morphine administration on the fetal production of oxytocin in labour
Authors: LINDOW S. W. , HENDRICKS M. S. , THOMPSON J. W. , VAN DER SPUY Z. M. 
Published: August 2015

1.Animal and human work has indicated that maternal oxytocin secretion is under the control of endogenous opiates. Previous workers have described the fetal production of oxytocin in addition to maternal production. The study of the interaction between exogenously administered opiates and oxytocin secretion may give insight into the activity of any opiate-mediated regulatory mechanism of oxytocin secretion in the fetus. This study was designed to investigate the effect of an opiate (5 mg of morphine) given to the mother on the fetal production of oxytocin in labour.
2.Morphine was given by the attending clinicians for analgesic purposes to women in the first stage of labour. After delivery umbilical artery vein and maternal vein specimens were taken.
3.Four groups of patients were studied: women after normal vaginal delivery without analgesia in labour (n = 10); women after normal vaginal delivery who had morphine administration in the first stage of labour (n = 12); women who had an emergency Caesarean section in the first stage of labour (n = 11); women who had an elective Caesarean section at term who were not in labour (n = 11).
4.Oxytocin levels were measured by radioimmunoassay in the maternal vein, umbilical artery and umbilical vein specimens. Morphine was measured by radioimmunoassay in the umbilical vein specimens.
5.The umbilical artery minus vein concentration of oxytocin was calculated for each patient (A-V). There was no change in the umbilical (A-V) concentration of oxytocin if morphine had been given to the mother in labour; this applied to fetuses delivered vaginally or by Caesarean section. When the fetuses who were exposed to morphine were analysed separately, there was no correlation between the umbilical vein morphine concentration and the umbilical (A-V) oxytocin concentration either in Caesarean or vaginal deliveries.
6.Fetal oxytocin production was not affected by the maternal administration of morphine in the first stage of labour. This applies to the oxytocin production in the first and second stage of labour.
Effect of endothelin-1 on endothelium-derived vascular responsiveness in man
Authors: KRUM Henry , CRANSWICK Noel , PELLIZZER Anne-Marie 
Published: August 2015

1.Endothelium-dependent vasodilatation via nitric oxide in response to muscarinic stimulation is decreased in chronic heart failure while basal release of nitric oxide may be increased. As production of the endothelium-derived vasoconstrictor endothelin-1 is increased in chronic heart failure, endothelin-1 may act in an autocrine manner to modulate these effects.
2.To test this, we determined whether prolonged endothelin infusion in normal subjects would reproduce the alterations in basal and stimulated nitric oxide release observed in patients with chronic heart failure. Basal nitric oxide production was determined by measurement of forearm blood flow using strain gauge venous occlusion plethysmography before and after brachial artery infusion of a nitric oxide synthase inhibitor (NG-monomethyl-l-arginine). Stimulated nitric oxide production was determined by brachial artery infusion of acetylcholine. As metabolic vasodilatation is thought to be mediated in part via nitric oxide and is decreased in chronic heart failure, forearm blood flow during peak reactive hyperaemia was also measured. Studies were then repeated during brachial artery infusion of endothelin-1 and a non-specific vasoconstrictor, noradrenaline.
3.Neither basal nor stimulated nitric oxide production was altered by endothelin-1 and noradrenaline infusion. However, absolute forearm blood flow responses to peak reactive hyperaemia were decreased during infusion of endothelin-1 in comparison to noradrenaline. These data suggest that increased endothelin-1 may not contribute greatly to altered basal and stimulated nitric oxide production in patients with chronic heart failure but may contribute to impaired metabolic vasodilatation, by mechanisms presumably unrelated to altered nitric oxide production.
Effect of salt-loading on blood pressure, insulin sensitivity and limb blood flow in normal subjects
Authors: FOO M. , DENVER A. E. , COPPACK S. W. , YUDKIN J. S. 
Published: August 2015

1.The aim of this study was to determine the effects of high (220 ;mmol/day) and low (40 ;mmol/day) salt intake for 6 days on blood pressure, leg blood flow and insulin sensitivity in 18 ;healthy normotensive subjects.
2.Twenty-four-hour ambulatory blood pressure was measured at baseline, during salt-loading and salt-depletion. Insulin sensitivity was determined by a two-step euglycaemic–hyperinsulinaemic clamp (low and high insulin infusion rates: 40 and 600 ;m-unit·min-1·m-2 respectively) and leg blood flow by plethysmography.
3.Salt-loading resulted in changes in weight [change between salt-loading and salt-restriction: δ =+0.45 (S.D.±0.69) ;kg, P = 0.015], plasma renin [δ =-11.5 (S.D.±12.9) ;μ-units/l, P = 0.001] and urinary noradrenaline [δ =-8.6 (S.D.±18.7) ;nmol/mmol creatinine, P = 0.05]. There were borderline significant increases in 24-h systolic blood pressure [δ =+5.8 (S.D.±14.2) mmHg, P = 0.06] and plasma volume [δ =+0.29 (S.D.±0.67) litres, P = 0.08].
4.Insulin sensitivity was similar in both salt states. Geometric mean metabolic clearance rate of low-dose insulin: low salt, 5.13 (S.D.×/÷1.35) dl/min; high salt, 4.94 (S.D.×/÷1.37) dl/min, P = 1.0. Geometric mean metabolic clearance rate of high-dose insulin: low salt, 9.68 ;dl/min (S.D.×/÷1.30); high salt, 9.68 (S.D.×/÷1.27) dl/min, P = 0.69.
5.Leg blood flow response to high-dose insulin on high salt increased significantly compared with low salt. Percentage change of blood flow on low salt, δ =+36.6 (S.D.±22.9)% versus high salt, δ =+66.8 (S.D.±52.2)%, P = 0.03.
6.There were no significant relationships between salt-related changes in limb blood flow and changes in insulin sensitivity at either insulin infusion rate.
7.We conclude that salt-loading, despite changing body weight, the renin–angiotensin–aldosterone system, urinary noradrenaline and the leg blood flow response to insulin, has no significant effect on insulin sensitivity. Salt-loading causes dissociated effects on insulin-induced vasodilatation and glucose disposal.
Inter-α-inhibitor in calcium stones
Authors: DAWSON Caroline J. , GROVER Phulwinder K. , KANELLOS Jerry , PHAM Hung , KUPCZYK Gosia , OATES Adrian , RYALL Rosemary L. 
Published: August 2015

1.A broad spectrum of proteins has been detected within calcium stones. A newcomer to the field of urolithiasis is the blood protein inter-α-inhibitor. Inter-α-inhibitor comprises three protein chains linked by chondroitin sulphate: two heavy chains, H1 (65 ;kDa) and H2 (70 ;kDa) and a light chain (approx. 30 ;kDa) most commonly known as bikunin. The physiological function of the two heavy chains is unknown; nor has their presence been reported in urine. However, bikunin has been implicated in various renal diseases, including urolithiasis.
2.This study was undertaken to determine which chains of inter-α-inhibitor are actually present in calcium kidney stones. Organic extracts were obtained from 10 calcium stones and analysed by SDS/PAGE and Western blotting. The H1 and H2 chains of inter-α-inhibitor were detected in 9 of the 10 stones, but only one stone contained a protein with a molecular mass close to that of bikunin (30–35 ;kDa).
3.These results demonstrate for the first time that H1 and H2 are present in stones and show that the bikunin chain of inter-α-inhibitor may not be the only part of the molecule implicated in stone formation.
Lack of habituation of the pattern of cardiovascular response evoked by sound in subjects with primary Raynaud's disease
Authors: EDWARDS Clare M. , MARSHALL Janice M. , PUGH M. 
Published: August 2015

1.The vasospasm of primary Raynaud's disease can be triggered by acute emotional stress. We have studied the pattern of cardiovascular response evoked by acute emotional stress, a sound stimulus of 90 ;dB, 2 ;kHz for 30 ;s, in eight subjects with primary Raynaud's disease and in eight age- and sex-matched controls, the sound being repeated five times on each of days 1, 3 and 5.
2.In controls, the first sound evoked the pattern of the alerting response that is characteristic of acute emotional stress: a rise in arterial pressure and heart rate, a decrease in vascular conductance in the cutaneous circulation of the digit, assessed by laser Doppler recording of erythrocyte (red cell) flux in the digit divided by arterial pressure, and an increase in forearm muscle vascular conductance, assessed from forearm blood flow recorded by venous occlusion plethysmography divided by arterial pressure.
3.In the subjects with primary Raynaud's disease, baselines of arterial pressure, digital cutaneous vascular conductance and forearm vascular conductance were not significantly different from those of the controls and they too showed the alerting response to the first sound, the magnitudes of the changes being comparable to those of the controls.
4.In both the controls and subjects with primary Raynaud's disease, the evoked responses were consistent on repetition of the sound on day 1. In contrast, judging from the means of the changes evoked on each day, the controls showed habituation of the individual components of the alerting response over days 1, 3 and 5, whereas the subjects with primary Raynaud's disease showed no habituation of either the forearm muscle vasodilatation or the digital vasoconstriction. Conversely, the decrease in digital cutaneous vascular conductance evoked by a single deep breath was fully reproducible in both controls and subjects with primary Raynaud's disease when tested at the beginning and end of each experimental day.
5.These results allow the novel conclusion that subjects with primary Raynaud's disease have an abnormality of the central neural modulation of the brain stem areas that integrate the cardiovascular components of the alerting response to acute emotional stress, such that habituation of the vasodilator and vasoconstrictor components of the response on repetition of the stimulus is impaired. We propose that such persistence of vasoconstrictor responses to stressful stimuli predisposes to vasospasm, particularly if neurally mediated vasoconstriction is reinforced by locally released vasoconstrictor factors.
Beneficial effect of vitamin E administration on nitric oxide function in subjects with hypercholesterolaemia
Authors: GREEN Daniel , O'DRISCOLL Gerry , RANKIN James M. , MAIORANA Andrew J. , TAYLOR Roger R. 
Published: August 2015

1.Vitamin E administration improves endothelial function in hypercholesterolaemic animals but, generally, has not been found to do so in man. The aim of this study was to determine whether vitamin E administration improves basal or stimulated function of the nitric oxide (·NO) dilator system in patients with hypercholesterolaemia.
2.Seven subjects aged 47±3 (±S.E.M.) years with moderately elevated serum cholesterol concentrations (6.0±0.1 ;mmol/l) were given 4 weeks of placebo therapy followed by 500 i.u. of vitamin E twice daily for 4 weeks. Endothelium-dependent and -independent vasodilatation were assessed by intrabrachial infusion of acetylcholine and sodium nitroprusside, and forearm blood flow was measured by strain-gauge plethysmography. Basal ·NO function was assessed by infusion of NG-monomethyl-l-arginine.
3.Plasma α-tocopherol concentration was enhanced after administration of vitamin E (34.6±1.8 to 86.9±9.6 ;μmol/l; P< 0.001). In addition, vitamin E administration significantly increased acetylcholine-mediated vasodilatation whether the results were expressed in terms of changes in absolute forearm blood flow (P< 0.01), forearm vascular resistance (P< 0.05) or forearm blood flow ratios (P< 0.001). Similarly, absolute forearm blood flow (P< 0.05), forearm vascular resistance (P< 0.01) and forearm blood flow ratio (P< 0.01) responses to NG-monomethyl-l-arginine were augmented by vitamin E therapy. Sodium nitroprusside responses were unaltered.
4.These results indicate that 4 weeks therapy with 1000 i.u. of vitamin E daily improves basal and stimulated ·NO-related endothelial function in subjects with hypercholesterolaemia.