bluuebunny/crossref_metadata_2025_split huggingface dataset:
Just How Big is the Pulmonary Granulocyte Pool?
Authors: Peters A. M. 
Published: August 2015

1. It is widely believed that a large fraction of the blood granulocyte population is located in the pulmonary circulation.
2. Evidence in favour of this belief is based on several independent and complementary techniques including studies of granulocyte deformability in relation to pulmonary capillary diameter, isolated perfused lungs, direct videomicroscopic observations, cellular and capillary morphometry, physiological studies and labelled blood cell kinetics.
3. Inconsistencies in this body of evidence can be identified and traced in many cases to doubts concerning the physiological integrity of labelled granulocytes.
4. In addition to the lungs, other regions of the body undoubtedly pool granulocytes, and there is good quantitative evidence, based mainly on clinical studies, pointing to the liver, bone marrow and especially the spleen.
5. Clinical studies, furthermore, have generally not supported major granulocyte pooling in the lung, except in association with systemic inflammatory diseases, such as inflammatory bowel disease and systemic vasculitis.
6. Compromises based on technical considerations permit reconciliation of the literature, and an overall whole-body model of granulocyte distribution is proposed with which all the existing data are broadly compatible.
Membrane Microviscosity and Plasma Triacylglycerols in the Rat
Authors: Devynck Marie-Aude , Kuneš J. , Le Quan Sang Kim Hanh , Zicha J. 
Published: August 2015

1. Multiple cell membrane alterations have been described in humans and animals with various genetic forms of hypertension and/or dyslipidaemia. The aim of our study was to characterize membrane microviscosity, using two different fluorescent probes exploring either the outer membrane leaflet [trimethylamino-diphenylhexatriene (TMA-DPH)] or the lipid membrane core [diphenylhexatriene (DPH)], in platelets and erythrocytes of genetically hypertensive rats of the Prague hereditary hypertriglyceridaemic (HTG) strain. The relationships of membrane microviscosity to hypertension, hypertriglyceridaemia and cell calcium handling were also investigated.
2. Membrane microviscosity was similar in HTG and normotensive control Wistar rats when measured in platelets or erythrocyte ghosts incubated in Na+-containing medium. On the contrary, TMA-DPH fluorescence anisotropy was significantly reduced in HTG platelets incubated in Na+-free medium because external Na+ removal elicited a larger rise of TMA-DPH anisotropy in Wistar platelets.
3. Plasma triacylglycerols were associated positively with platelet TMA-DPH anisotropy and negatively with DPH anisotropy in both strains. The slopes of these relationships were reduced in HTG compared with Wistar rats. Platelet TMA-DPH anisotropy correlated positively and DPH anisotropy negatively with the cytosolic calcium concentration in unstimulated platelets, the slopes being almost identical in both strains.
4. Pulse pressure correlated negatively with TMA-DPH anisotropy and positively with DPH anisotropy found in erythrocyte ghosts.
5. The present results suggest that plasma triacylglycerols and cytosolic calcium are capable of modulating the membrane microviscosity in this new animal model of genetic hypertension associated with hypertriglyceridaemia.
Angiotensin-Converting Enzyme Inhibition Does Not Correct Early Defects in Renal and Vascular Permeability in Diabetes Mellitus
Authors: Zietse Robert , Derkx Frans H. , Weimar Willem , Schalekamp Maarten A. 
Published: August 2015

1. In diabetes mellitus a selective increase in the excretion of albumin generally precedes the occurrence of demonstrable loss of glomerular size-selectivity. However, even in this (microalbuminuric) phase of diabetic nephropathy a defect in glomerular barrier function can be demonstrated during infusion of atrial natriuretic peptide.
2. The aim of this study was to investigate whether angiotensin-converting enzyme inhibition could prevent the proteinuric response to atrial natriuretic peptide in these patients. We performed infusions of atrial natriuretic peptide (0.01 μg min−1 kg−1) in 10 patients with insulin-dependent diabetes mellitus and microalbuminuria (urinary albumin excretion 90 ± 44 mg/day), both before and after 1 month of treatment with enalapril (20 mg once daily).
3. Despite a 40% reduction in proteinuria, angiotensin-converting enzyme inhibition did not prevent the atrial natriuretic peptide-induced increase in protein excretion. Both before and during angiotensin-converting enzyme inhibition, atrial natriuretic peptide infusion resulted in a significant increase in the fractional excretion of large dextran molecules, which is compatible with an increase in flow through large unrestrictive ‘shunt' pores. Atrial natriuretic peptide infusion also induced an increase in the transcapillary escape rate of albumin and angiotensin-converting enzyme inhibition also failed to prevent this effect of atrial natriuretic peptide on peripheral capillary permeability.
4. We conclude that angiotensin-converting enzyme inhibition during 1 month does not correct the capillary barrier function defect in patients with diabetes mellitus and microalbuminuria that is unmasked by atrial natriuretic peptide infusion.
Systemic Nitric Oxide Synthase Inhibition Increases Insulin Sensitivity in Man
Authors: Butler R. , Morris A.D. , Struthers A. D. 
Published: August 2015

1. Recent evidence shows that skeletal muscle blood flow is an important determinant of insulin sensitivity and that insulin-mediated vasodilatation is nitric oxide dependent. These results have given rise to the hypothesis that endothelial nitric oxide inhibition may decrease insulin sensitivity in humans.
2. We examined this hypothesis directly by evaluating the effects of systemic nitric oxide synthase inhibition with NG-monomethyl l-arginine (3 mg h−1 kg−1) on whole-body glucose uptake (euglycaemic hyperinsulinaemic clamp) and calf blood flow (bilateral calf venous occlusion plethysmography) in 16 healthy male subjects in a randomized, double-blind, placebo-controlled, crossover study.
3. NG-Monomethyl l-arginine infusion was associated with a pressor effect (119/61 ± 2/2 compared with 114/58 ± 2/2 mmHg for placebo; P &lt; 0.001), and a negative chronotropic response (57 ± 2 compared with 62 ± 2 beats/min for placebo; P &lt; 0.001). The glucose infusion rate was significantly increased after infusion of NG-monomethyl l-arginine (8.9 ± 0.9 compared with 7.9 ± 0.8 mg min−1 kg−1 for placebo; P = 0.002). Whole-body glucose uptake increased during the clamp, with values of 9.4 ± 0.7 and 10.9 ± 0.8 mg min−1 kg−1 for placebo and NG-monomethyl l-arginine respectively (P = 0.036; 95% confidence interval 0.2,2.8). NG-Monomethyl l-arginine was associated with increased calf blood flow by comparison with placebo (P &lt; 0.05, area under curve).
4. These data show for the first time that systemic inhibition of nitric oxide synthesis increases rather than decreases whole-body glucose uptake. We suggest that the higher skeletal muscle blood flow seen after NG-monomethyl l-arginine may explain the observed increase in whole-body glucose uptake.
Pancreatic Bile-Salt-Dependent Lipase Activity in Serum of Diabetic Patients: Is There a Relationship with Glycation?
Authors: Caillol Nathalie , Pasqualini Eric , Mas Eric , Guieu Régis , Valette Anne , Boyer Jean , Lombardo Dominique 
Published: August 2015

1. Pancreatic bile-salt-dependent lipase has been detected in human plasma where it has the capability to modify normal low- and high-density lipoprotein composition and structure and to reduce the atherogenicity of oxidized low-density lipoprotein (Shamir R, Johnson WJ, Morlock-Fitzpatrick K, Zolfaghari R, Li L, Mas E, Lombardo D, Morel DW, Fisher EA. Pancreatic carboxyl ester lipase: a circulating enzyme that modifies normal and oxidized lipoproteins in vitro. J Clin Invest 1996; 97: 1696–704).
2. In the present study, we investigated the effect of glycation and particularly that of human serum albumin on the activity of bile-salt-dependent lipase. In vitro, bile-salt-dependent lipase activity decreased in the presence of human serum albumin; however, this was less pronounced in the presence of glycated human serum albumin. In vivo, bile-salt-dependent lipase specific activity was about 2-fold higher in the sera of diabetic patients than in the sera of normal subjects.
3. A significant increase in the specific activity of bile-salt-dependent lipase related to the serum level of glycation was observed. The increase in bile-salt-dependent lipase specific activity was not related to the glucose concentration in serum suggesting that glycation of bile-salt-dependent lipase could not be involved in the observed effects. Although the stability of serum bile-salt-dependent lipase was important enough to allow a systemic action of the enzyme on lipoproteins, it could not explain the higher activity of the enzyme in diabetic serum.
4. We concluded that bile-salt-dependent lipase could be helpful against the premature development of atherosclerosis in diabetes.
Metabolic and Myoelectrical Effects of Acute Hypoxaemia during Isometric Contraction of Forearm Muscles in Humans: A Combined 31P-Magnetic Resonance Spectroscopy-Surface Electromyogram (MRS—SEMG) Study
Authors: Bendahan D. , Badier M. , Jammes Y. , Confort-Gouny S. , Salvan A. M. , Guillot C. , Cozzone P. J. 
Published: August 2015

1. Failure of muscle force during sustained fatiguing contraction is associated with myoelectrical and metabolic alterations. However, the inter-relationships between these two types of events remain unclear. The purpose of this study was to examine the effects of decreased oxygen availability during sustained contraction on myoelectrical and metabolic changes, thereby addressing the issue of fatigue.
2. 31P-Magnetic resonance spectra and surface electromyograms were simultaneously recorded in six subjects (three women and three men) performing isometric contraction of forearm flexor muscles sustained at 60% maximum value of force under aerobic or acute hypoxaemic conditions (inhalation of a gas mixture containing 12% O2).
3. The 5 min hypoxaemic rest preceding contraction did not affect the phosphocreatine level and pH value. Under both conditions of oxygen availability, the magnitude of metabolic changes remained similar and the duration of contraction was unaffected (similar workload). However, hypoxaemia significantly reduced the rate of changes in integrated surface electromyogram activity measured in the high-frequency band. Correlative analysis of magnetic resonance spectroscopy and surface electromyogram data shows that for a given surface electromyogram change, metabolic variations were always larger under hypoxaemic conditions.
4. These results suggest that hypoxaemia does not alter metabolic changes, i.e. decrease in pH and phosphocreatine during static contraction. The downward shift of the relationships between myoelectrical and metabolic changes under hypoxaemia points to the existence of a better excitation—contraction coupling in acute hypoxaemia compared with normoxia and this is indicative of an adaptative mechanism.
Early Administration of Angiotensin-Converting Enzyme Inhibitor Captopril, Prevents the Development of Hypertension Programmed by Intrauterine Exposure to a Maternal Low-Protein Diet in the Rat
Authors: Sherman Rachel C. , Langley-Evans Simon C. 
Published: August 2015

1. Associations of intrauterine exposure to maternal undernutrition with later hypertension and coronary heart disease in the human population have been duplicated in the rat. Fetal exposure to low protein diets produces offspring that develop raised systolic blood pressure by the age of weaning. This animal model of ‘programmed’ hypertension was used to investigate the role of the renin—angiotensin system in the initiation and maintenance of high blood pressure.
2. Pregnant rats were fed diets containing 18 or 9% casein from conception until littering. The offspring from these pregnancies were administered captopril either between 2 and 4 weeks of age, or from 10 to 12 weeks of age.
3. The feeding of low protein diets in pregnancy had no effect upon the reproductive ability of female rats and the offspring generated were of normal birthweight. By 4 weeks of age the male and female offspring of low-protein-fed dams had systolic blood pressures that were 24–25 mmHg higher than those of rats exposed to a control diet in utero.
4. Treatment of 10-week-old female offspring with captopril for 2 weeks indicated that angiotensin II formation may play a role in the maintenance of high blood pressure in low-protein-exposed rats. While captopril had no significant effect upon systolic pressures of rats exposed to the control diet in intrauterine life, the systolic blood pressures of low-protein animals rapidly declined by 31 mmHg.
5. Administration of captopril to male and female offspring between 2 and 4 weeks of age exerted long-term effects upon systolic blood pressure. Eight weeks after cessation of treatment, at an age where maximal blood pressures are achieved, captopriltreated, low-protein-exposed rats had similar blood pressures to normotensive rats exposed to the protein-replete diet in utero.
6. In conclusion, we have demonstrated that the elevation of adult blood pressure associated with fetal exposure to a maternal low-protein diet, is prevented by early administration of an angiotensin-converting enzyme inhibitor. The actions of angiotensin II in the late suckling period may be a critical determinant of long-term cardiovascular functions in these animals.
Human Muscle Sympathetic Activity and Cardiac Catecholamine Spillover: No Support for Augmented Sympathetic Noradrenaline Release by Adrenaline Co-Transmission
Authors: Thompson Jane M. , Wallin B. Gunnar , Lambert Gavin W. , Jennings Garry L. , Esler Murray D. 
Published: August 2015

1. Evidence from animal studies indicates that circulating adrenaline may be taken up into sympathetic nerves, facilitating the release of noradrenaline. To test whether adrenaline acts as a co-transmitter in humans we studied eight healthy men (aged 19–23 years) during isometric handgrip before and after an adrenaline infusion (1–3 μg/min for &gt; 30 rain). Sympathetic activity was assessed using radiotracer kinetic techniques to measure total and cardiac spillovers of noradrenaline and adrenaline, and microneurography to measure muscle sympathetic activity.
2. During the adrenaline infusion systolic blood pressure and heart rate increased significantly and diastolic blood pressure decreased. Total noradrenaline spillover, and arterial and coronary sinus plasma noradrenaline concentrations, increased significantly. Muscle sympathetic nerve traffic increased both during and after the end of the infusion.
3. Thirty minutes after the end of the adrenaline infusion there was adrenaline release from the heart (1.5 ± 0.4 ng/min, mean ± S.E.M.) indicating that significant adrenaline loading of cardiac sympathetic nerves had occurred. At this time muscle sympathetic nerve traffic and total body and cardiac noradrenaline spillovers were similar (P &gt; 0.05) to pre-adrenaline infusion values (nerve traffic 24 ± 4 versus 21 ± 3 bursts/min; total noradrenaline spillover 698 ± 98 versus 618 ± 119 ng/min; cardiac noradrenaline spillover 16.2 ± 2.8 versus 13.9 ± 3.9 ng/min).
4. Isometric handgrip contraction evoked similar responses pre- and post-adrenaline infusion in total and cardiac noradrenaline spillovers and in muscle sympathetic activity.
5. The results do not support the theory that adrenaline is a co-transmitter facilitating noradrenaline release from human sympathetic nerves.
Time Course and Pattern of Pulmonary Flow Distribution following Unilateral Airway Occlusion in Sheep
Authors: Johansen B. , Melsom M. N. , Flatebø T. , Nicolaysen G. 
Published: August 2015

1. Unilateral bronchial occlusion causes ipsilateral hypoxic pulmonary vasoconstriction, which shifts blood flow towards the other lung. We studied the time course of flow diversion following acute bronchial occlusion, and the temporal effect of the latter on blood gases and vertical distribution of blood flow within the two lungs.
2. Serial infusions of radioactive or fluorescent microspheres were given to each of seven adult standing sheep before, during occlusion of the left mainstem bronchus for up to 6 min, and after release of occlusion. Pulmonary and systemic arterial pressures were recorded continuously and arterial and mixed venous blood gases were determined intermittently. Post-mortem, the lungs were inflated, dried and cut into slices. Relative blood flow at the time of infusion was expressed as the weight-normalized intensity of each tracer in each slice or lung divided by the weight-normalized intensity in the two lungs.
3. Within 30 s, 1 min and 2 min after onset of occlusion, flow in the occluded lung had decreased to 68–84% (range), 51–78% and 43–79% respectively, of the initial value. In the contralateral lung, flow increased by 10–24%, 14–37% and 23–39% respectively. The distribution of flow along the gravitational axis within each lung varied widely between animals, both before and during occlusion. The during-occlusion profiles in the occluded lung differed from those in the non-occluded lung. In either lung, during-occlusion profiles could not be predicted with certainty from the pre-occlusion profiles. Two minutes post-occlusion, inter- and intra-lung flow distribution were nearly the same as before occlusion. Arterial oxygen tension fell in the first minute of occlusion, but never below 7.5 kPa, and increased slowly thereafter. Arterial carbon dioxide tension increased slightly throughout the occlusion period. No appreciable changes in systemic or pulmonary artery pressure were observed. Post-occlusion, arterial oxygen tension was still sub-normal, while carbon dioxide tension continued to increase.
4. We conclude that acute unilateral bronchial occlusion diverts blood flow within 30 s towards the contralateral lung. This rapidly occurring flow diversion prevents the development of severe arterial hypoxaemia. The variable and largely unpredictable distribution of blood flow in the hyperfused non-occluded lung might explain some of the gas-exchange abnormalities observed in physiologically hyperfused lungs and in patients with one hyperfused lung.
Haemodynamic Responses in Young and Elderly, Healthy Subjects during Ambient and Warm Head-up Tilt
Authors: Lye Michael , Walley Tom 
Published: August 2015

1. Postural hypotension is common in elderly people and is usually multifactorial in origin. In young subjects increased ambient temperature is associated with postural symptoms. We hypothesized that such increases in skin temperature due to the use of bed clothes might contribute to nocturnal postural hypotension in the elderly. We therefore studied haemodynamic responses to head-up tilt in healthy elderly and young subjects, with and without passive heating induced by covering with blankets.
2. Nine young (28.7 ± 1.5 years; mean ± S.E.M.) and nine elderly (71.9 ± 1.8 years) subjects were studied. All had been carefully screened to exclude factors likely to affect responses to tilt. All subjects underwent a standard head-up tilt procedure at ambient room temperature while haemodynamic responses were monitored. The subjects were then covered in blankets for 55 min and the tilt repeated. Skin temperature before the second tilt had increased from approximately 32.5 °C to approximately 35.2 °C (P &lt; 0.001).
3. The elderly subjects maintained higher blood pressures throughout both tilts (P &lt; 0.001) and both groups showed similar qualitative responses to tilt. Supine heart rates were higher in the elderly group (P &lt; 0.01) with a tendency to increase more in the young group in response to tilt, especially while warm (P = 0.370). Stroke volumes and cardiac indices were consistently higher in the young group who showed larger changes during both head-up tilts. In both groups the haemodynamic responses to ambient and warm tilt were essentially the same.
4. Healthy elderly subjects, who are carefully screened to exclude individuals with cardiovascular pathology, respond to head-up tilt in the same qualitative fashion as young subjects. Quantitative responses in older subjects are ‘damped’. Short-term natural body warming does not impair the reflexes in young or old subjects.
Vasopressin V1a and V2 Receptor mRNA in Deoxycorticosterone Acetate-Salt Hypertension in the Rat
Authors: Risvanis J. , Johnston C. I. , Phillips P. A. , Burrell L. M. 
Published: August 2015

1. Vasopressin V1a and V2 receptors are differentially regulated in deoxycorticosterone acetate-salt hypertension. This paper investigated whether the changes were due to transcription changes in receptor mRNA assessed by in situ hybridization histochemistry (liver V1a receptor) and by reverse transcription—polymerase chain reaction (kidney V1a and V2 receptor).
2. Systolic blood pressure and plasma vasopressin levels were significantly elevated in deoxycorticosterone acetate-salt rats (n = 24) compared with water-control (n = 28) and salt-control rats (n = 28) (P &lt; 0.001). Plasma sodium was elevated in deoxycorticosterone acetate-salt rats compared with both control groups (P &lt; 0.01) and plasma osmolality was elevated in deoxycorticosterone acetate-salt rats compared with water-control rats (P &lt; 0.05).
3. Binding kinetic studies demonstrated downregulation of liver V1a and kidney V2 receptors in deoxycorticosterone acetate-salt rats compared with water-control and salt-control rats (P &lt; 0.05). This was not associated with any change in liver V1a receptor mRNA (P = 0.95), or in kidney V1a (P = 0.79) or V2 receptor mRNA (P = 0.96).
4. In deoxycorticosterone acetate-salt hypertension, downregulation of liver V1a and kidney V2 receptors occurs in the setting of stable vasopressin gene transcription. These results suggest that changes in receptor processing may be responsible for the differential regulation of vasopressin receptors that occurs in deoxycorticosterone acetate-salt hypertension.
Serum total sialic acid, a reputed cardiovascular risk factor, and its relationship to lipids, plasma fasting insulin, blood pressure and body mass index in normal individuals
Authors: CROOK M. , LUMB P. , ANDREWS V. , SWAMINATHAN R. 
Published: August 2015

1.Serum sialic acid is a reputed cardiovascular risk factor, but the reason why this is so is not clear. We therefore studied its relationship with other known cardiovascular risk factors (particularly those associated with insulin resistance) in 100 healthy young subjects (54 females and 46 males, age 20.7±0.89 years).
2.There was a significant univariate correlation between serum total sialic acid and fasting plasma insulin. Serum total sialic acid also correlated with fasting plasma glucose concentration and serum cholesterol and triacylglycerol.
3.In females there was a strong univariate correlation between serum total sialic acid and plasma fasting insulin and glucose concentrations, although in males there was a weaker univariate correlation between serum total sialic acid and fasting plasma glucose and the insulin resistance index. In addition, serum total sialic acid significantly correlated with systolic blood pressure, fasting serum cholesterol and triacylglycerol concentrations and body mass index in the females. In males serum total sialic acid significantly positively correlated with fasting serum cholesterol and triacylglycerol concentrations, and correlated inversely with the hip/waist ratio.
4.In multiple regression analysis of the 100 subjects serum total sialic acid correlated independently with fasting serum cholesterol, glucose and also plasma insulin concentrations. In females serum total sialic acid independently correlated with systolic and diastolic blood pressure, and serum cholesterol and fasting plasma glucose concentrations, although there was no significant independent correlation between serum total sialic acid and any of the other variables in the males.