bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effects of Sodium Status on the Venous Response to Noradrenaline Infusion in Pre-Ascitic Cirrhosis
Authors: Wong Florence , Bomzon Arieh , Logan Alexander , Blendis Laurence 
Published: August 2015

1. This study assesses the effects of sodium status on venous responsiveness to noradrenaline and the neurohumoral profile in pre-ascitic cirrhotic patients. Eight cirrhotic patients and ten control subjects were studied after both a low (20 mmol/day) and a high (200 mmol/day) sodium diet. Venous responsiveness to increasing doses of noradrenaline in a dorsal hand vein and various plasma hormone levels were measured. Maximal response (Rmax.) and the dose of noradrenaline that yielded 50% of Rmax (ED50) were then calculated.
2. A significantly smaller dorsal hand vein diameter was observed in the control subjects on a low sodium (2.23 ± 0.14 mm) compared with a high sodium (2.57 ± 0.15 mm; P = 0.04) diet, but not in the cirrhotic patients. Rmax. was not significantly different in either group on both diets. With low sodium intake, ED50 was similar in the two groups. However, on high sodium intake, control subjects had a significantly higher ED50 (34.4 ± 7.4 ng/min) than the cirrhotic patients (5.03 ± 0.86 ng/min; P &lt; 0.003). Plasma noradrenaline in the control subjects fell significantly with the change from a low (1.29 ± 0.11 nmol/l) to a high (0.68 ± 0.09 nmol/l; P &lt; 0.001) sodium diet, but remained elevated in the cirrhotic patients. Cirrhotic patients had significantly higher atrial natriuretic factor levels and lower plasma renin activity than the control subjects on both diets.
3. In conclusion, pre-ascitic cirrhotic patients show no evidence of venodilatation. Their sympathetic nervous activity is not suppressible by volume expansion. Relative hyper-responsiveness of the peripheral venous circulation to adrenergic stimulation with high sodium intake is present.
Effect of Blockade of Nitric Oxide Synthesis on the Renin Secretory Response to Frusemide in Conscious Rabbits
Authors: Reid Ian A. , Chou Lance 
Published: August 2015

1. The enzyme nitric oxide synthase is present in the macula densa and may participate in the control of renin secretion by the adjacent juxtaglomerular cells. In the present study, we investigated the effect of inhibiting nitric oxide synthase on the renin secretory response to frusemide, which stimulates renin secretion by blocking Na+-K+-2Cl− co-transport in the macula densa.
2. Injection of frusemide in 12 conscious rabbits elicited a transient increase in mean arterial pressure from 84 ± 2 to 92 ± 3 mmHg at 5 min (P &lt; 0.01) and a sustained increase in heart rate from 246 ± 6 to 281 ± 10 beats/min at 45 min (P &lt; 0.01). Plasma renin activity increased from 8.0 ± 1.2 to 14.3 ± 1.8, 12.4 ± 1.6 and 11.6 ± 1.5 pmol 2 h−1 ml−1 at 15, 30 and 45 min respectively (P &lt; 0.01). There were no changes in plasma sodium and potassium concentrations or osmolality.
3. Inhibition of nitric oxide synthase with NG-nitro-l-arginine methyl ester increased mean arterial pressure by 9 mmHg, decreased heart rate and plasma renin activity, and markedly suppressed the renin response to frusemide (from 4.6 ± 0.7 to 7.6 ± 1.7, 4.7 ± 1.0 and 4.6 ± 0.7 pmol 2 h−1 ml−1 at 15, 30 and 45 min respectively). By contrast, infusion of an equipressor dose of phenylephrine did not suppress the renin response to frusemide.
4. Histochemical studies with the NADPH diaphorase technique confirmed the presence of nitric oxide synthase in the macula densa, and suggested that enzyme activity is increased by treatment with frusemide.
5. These results are consistent with a role for the l-arginine—nitric oxide pathway in the modulation of renin secretion by the macula densa.
Intracranial Pressure at High Altitude and Acute Mountain Sickness
Authors: Wright A. D. , Imray C. H. E. , Morrissey M. S. C. , Marchbanks R. J. , Bradwell A. R. 
Published: August 2015

1. Raised intracranial pressure has been noted in severe forms of acute mountain sickness and high-altitude cerebral oedema, but the role of intracranial pressure in the pathogenesis of mild to moderate acute mountain sickness is unknown.
2. Serial measurements of intracranial pressure were made indirectly by assessing changes in tympanic membrane displacement in 24 healthy subjects on rapid ascent to 5200 m.
3. Acute hypoxia at 3440 m was associated with a rise in intracranial pressure, but no difference was found in pressure changes at 4120 or 5200 m in subjects with or without symptoms of acute mountain sickness.
4. Raised intracranial pressure, though temporarily associated with acute hypoxia, is not a feature of acute mountain sickness with mild or moderate symptoms.
Effects of Endopeptidase 24.11 Inhibition on Plasma and Tissue Concentrations of Vasoactive Intestinal Peptide
Authors: Duggan K. A. , Jones D. M. , Ye V. Z. C. , Davis R. E. , MacDonald G. J. 
Published: August 2015

1. In this study, we sought to determine the effect of endopeptidase 24.11 inhibition on the rate of metabolism of vasoactive intestinal peptide. The effect of such inhibition on the concentration of vasoactive intestinal peptide in two tissues was also investigated.
2. Male Sprague—Dawley rats were given the endopeptidase 24.11 blocker UK77,568 (10 mg/kg) or vehicle as a single intravenous injection or as a daily injection for 4 days. Two hours after the final or single injection, the rats were anaesthetized and blood was sampled to determine plasma concentrations of vasoactive intestinal peptide and angiotensin II. The hearts and kidneys were harvested and snap-frozen in liquid nitrogen. The plasma and tissue concentrations of vasoactive intestinal peptide and the plasma concentration of angiotensin II were determined by radioimmunoassay. In a separate group of experiments, male Sprague—Dawley rats were anaesthetized and carotid and jugular catheters were inserted. One hour after intravenous administration of UK77,568 or vehicle, an infusion of vasoactive intestinal peptide (10 pmol min−1 kg−1) was commenced via the jugular catheter. Blood was sampled to determine the vasoactive intestinal peptide concentration 1 h after commencing the vasoactive intestinal peptide infusion to calculate the metabolic clearance rate.
3. Plasma vasoactive intestinal peptide increased after acute (P &lt; 0.05) but not chronic administration of UK77,568, while the concentration of vasoactive intestinal peptide in the heart increased after chronic administration (P &lt; 0.0005). The concentration of vasoactive intestinal peptide in the kidney was unchanged after both acute and chronic endopeptidase 24.11 blockade. Plasma angiotensin II decreased significantly in the chronic group (P &lt; 0.05). The metabolic clearance rate of vasoactive intestinal peptide decreased significantly after UK77,568 administration (P &lt; 0.05).
4. These studies add to the existing indirect evidence that endopeptidase 24.11 may metabolize vasoactive intestinal peptide in addition to a number of other hormones.
Whole-Body Protein Turnover and Hepatic Protein Synthesis Are Increased by Vaccination in Man
Authors: Cayol M. , Tauveron I. , Rambourdin F. , Prugnaud J. , Gachon P. , Thieblot P. , Grizard J. , Obled C. 
Published: August 2015

1. The ability of diphtheria—tetanus—poliomyelitis—typhoid vaccination to induce modifications in protein metabolism was investigated in post-absorptive healthy humans.
2. Seven subjects were studied before and 2 days after vaccination. They underwent an intravenous primed constant infusion of l-[1-13C]leucine for 4 h. Plasma protein concentrations, whole-body amino acid fluxes and acute-phase protein synthesis were determined.
3. Plasma concentrations of fibrinogen, α1-acid glycoprotein, haptoglobin and α1-antitrypsin were significantly elevated 2 days after vaccination (P &lt; 0.05). Leucine oxidation was unaffected but whole-body protein synthesis and breakdown were both increased (P &lt; 0.05), by 25 and 16% respectively, in subjects who had an elevated body temperature (n = 5). Albumin synthesis was unchanged, but hepatic synthesis of fibrinogen was 56% higher after vaccination.
4. The present investigation indicates that diphtheria—tetanus—poliomyelitis—typhoid vaccination could induce a sustained acute-phase reaction. Moreover, protein metabolism appeared to be extremely sensitive to a mild stress since leucine kinetics and fibrinogen synthesis were affected. Therefore, diphtheria—tetanus—poliomyelitis—typhoid vaccination might represent an attractive model for studying the inflammatory process in humans.
Effects of Weight Reduction on the Regulation of Lipolysis in Adipocytes of Women with Upper-Body Obesity
Authors: Reynisdottir Signy , Langin Dominique , Carlström Kjell , Holm Cecilia , Rössner Stephan , Arner Peter 
Published: August 2015

1. The regulation of lipolysis was studied in 14 upper-body obese women aged 26–55 years. Isolated subcutaneous adipocytes from the abdominal region were examined before and after an 8 to 12-week-long weight reduction programme, during which the mean body mass index (kg/m2) of the group was reduced from 36.4 ± 0.9 to 30.3 ± 1.0.
2. Fat cell volume was reduced from 891 ± 39 to 655 ± 45 pl. The sensitivity to noradrenaline stimulation of lipolysis in vitro increased fivefold after weight reduction. A corresponding increase in sensitivity was found with the β2-selective adrenoceptor agonist terbutaline. However, the number of β2-adrenoceptor binding sites as assessed by radioligand binding with 125I-labelled cyanopindolol was not changed. No changes were observed when dobutamine (a β1-selective adrenoceptor agonist) and clonidine (an α2-adrenoceptor agonist) were used.
3. The basal lipolysis rates decreased by about 50% after weight reduction and the maximum enzyme activity of hormone-sensitive lipase was also reduced by almost 50%.
4. Plasma concentrations of insulin, noradrenaline and total testosterone decreased and sex hormone-binding globulin increased after weight reduction. Calculated apparent free testosterone levels decreased by more than 40% after weight reduction.
5. In conclusion, weight reduction leads to increased efficiency of adipocyte lipolysis with decreased resting lipolysis rate but increased sensitivity to stimulation by catecholamines, which may be attributed to a decreased activity of hormone-sensitive lipase and an increased sensitivity of β2-adrenoceptors. Changes in circulating levels of catecholamines, insulin and testosterone may play a role in these modifications of adipocyte function. The increased lipolytic efficiency may be of importance for amelioration of the metabolic complications of obesity that are observed after weight reduction.
Calcitonin Gene-Related Peptide as An Endogenous Vasodilator: Immunoblockade Studies in Vivo with an Anti-Calcitonin Gene-Related Peptide Monoclonal Antibody and Its Fab′ Fragment
Authors: Tan Keith K. C. , Brown Morris J. , Hargreaves Richard J. , Shepheard Sara L. , Cook Deborah A. , Hill Raymond G. 
Published: August 2015

1. Calcitonin gene-related peptide (CGRP) is localized in perivascular sensory neurons and is a potent vasodilator. We investigated the utility of immunoblockade as an in vivo technique for probing the role of CGRP as an endogenous vasodilator.
2. The effects of an anti-CGRP monoclonal antibody (MAb; coded C4.19) and its Fab′ fragment on CGRP-induced changes in blood pressure and skin blood flow were studied in pentobarbitone-anaesthetized rats. Antidromic skin vasodilatation in the rat hind paw was measured by laser Doppler fluxmetry.
3. The dose—response relationship for the hypotensive effect of intravenous rat αCGRP (rαCGRP) was similarly shifted rightward by MAb C4.19 IgG (1 mg/rat; intravenously) and Fab′ fragment (2 mg/rat; intravenously). The C-terminal fragment of human αCGRP (hαCGRP8–37) also blocked the hypotensive effect of rαCGRP.
4. MAb C4.19 Fab′ fragment (2 mg/rat; intravenously) and hαCGRP8–37 (100 nmol/kg; intravenously), but not MAb C4.19 IgG (up to 3 mg/rat; intravenously) or normal mouse Fab′ fragment (2 mg/rat; intravenously), blocked the increased skin blood flow response to antidromic stimulation of the saphenous nerve.
5. The mean percentage changes in skin blood flow parameters due to MAb C4.19 Fab′ fragment were significantly different from those due to normal mouse Fab′ fragment (unpaired t-test; P &lt; 0.05) but not from those due to hαCGRP8–37.
6. The results demonstrate the pharmacokinetic advantage of Fab′ fragment over IgG for immunoblockade studies in vivo and support the role of CGRP in mediating skin vasodilatation.
Differential Effects of a Novel Non-Peptide Endothelin Receptor Antagonist (Bosentan) in Rat Liver and Vasculature
Authors: Phillips Paddy A. , Risvanis John , Aldred Kathryn , Burrell Louise M. , Bartholomeusz Briony 
Published: August 2015

1. We studied the effects of the non-selective, non-peptide, orally active endothelin (ET) receptor antagonist bosentan (Ro 47–0203) on rat hepatic and mesenteric vascular membrane 125I-ET-1 binding characteristics in vitro and ex vivo (after bosentan by gavage in vivo).
2. Bosentan caused a concentration-dependent competitive inhibition of 125I-ET-1 binding to female rat mesenteric vascular (predominantly ETA receptors) and hepatic (predominantly ETB receptors) membranes in vitro and ex viva
3. The time course of the inhibition of binding ex vivo after administration of bosentan in vivo was 1–4 h for mesenteric vascular (predominantly ETA receptors) binding and 1–16 h for hepatic (predominantly ETB receptors) binding.
4. The time course of displacement of 125I-ET-1 binding from mesenteric vascular and hepatic membranes by bosentan in vitro was similar.
5. Since bosentan is significantly excreted by the liver, the prolonged hepatic 125I-ET-1 binding by bosentan presumably represents hepatic accumulation of bosentan, which may have implications for bosentan antagonizing the actions of ET in the liver.
Intravenous Magnesium Sulphate Relieves Migraine Attacks in Patients with Low Serum Ionized Magnesium Levels: A Pilot Study
Authors: Mauskop Alexander , Altura Bella T. , Cracco Roger Q. , Altura Burton M. 
Published: August 2015

1. We tested the hypothesis that patients with an acute attack of migraine headache and low serum levels (&lt; 0.54 mmol/l) of ionized magnesium are more likely to respond to an intravenous infusion of magnesium sulphate (MgSO4) than patients with higher serum ionized magnesium levels.
2. Serum ionized magnesium levels were drawn immediately before infusion of 1 g of MgSO4 in 40 consecutive patients with an acute migraine headache.
3. Pain reduction of 50% or more as measured on a headache intensity verbal scale of 1 to 10, occurred within 15 min of infusion in 35 patients. In 21 patients, at least this degree of improvement or complete relief persisted for 24 h or more. Pain relief lasted at least 24 h in 18 of 21 patients (86%) with serum ionized magnesium levels below 0.54 mmol/l, and in 3 of 19 patients (16%) with ionized magnesium levels at or above 0.54 mmol/l (P &lt; 0.001). Mean ionized magnesium levels in patients with relief lasting for at least 24 h were significantly lower than in patients with no relief or brief relief (P &lt; 0.01).
4. Measurement of serum ionized magnesium levels may be useful in identifying patients with migraine headaches who may respond to an intravenous infusion of MgSO4.
Characteristics of the Sodium/Hydrogen Exchange in Non-Insulin-Dependent Diabetic Patients with Microalbuminuria and Hypertension
Authors: Zaidi K. Fatima , Yudkin John S. 
Published: August 2015

1. An association has been described between increased sodium/hydrogen (Na+/H+) exchange rates in various cells and microalbuminuria in type 1 diabetic patients. However, no data are available on the Na+/H+ exchange rate in type 2 diabetes and its association with urinary albumin excretion rates.
2. We have estimated platelet sodium-activated proton efflux (Na+/H+ exchange rate), based on a fluorimetric method, in 43 type 2 diabetic patients, of whom 29 were normoalbuminuric and 14 microalbuminuric, and in 10 non-diabetic control subjects. The factors measured were: buffering power, Km for external Na+ and Vmax. of the exchange rate.
3. There were no differences in Km and Vmax. for the Na+/H+ exchange between the subject groups. However, the 14 patients with microalbuminuria showed a significantly lower buffering capacity [17.2 (4.6) mmol l−1 pH unit−1] [mean (SD)] compared with non-diabetic control subjects [21.1 (1.9) mmol l−1 pH unit−1] (P = 0.020).
4. Among the 43 diabetic patients, 16 were hypertensive. These patients had similar characteristics of Na+/H+ exchange to the 27 normotensive diabetic patients and the control subjects.
5. There was no correlation between exchange rate variables of type 2 diabetic patients and fasting concentrations of insulin or albumin excretion rate.
6. We conclude that the platelets of microalbuminuric diabetic patients manifest a significantly lower buffering capacity. This lower buffering capacity may be due to abnormalities of other ion transport systems or to abnormalities in intermediary metabolism.
Effect of Angiotensin-Converting Enzyme Inhibitors on Resistance Artery Structure and Endothelium-Dependent Relaxation in Two-Kidney, One-Clip Goldblatt Hypertensive and Sham-Operated Rats
Authors: Bennett Michael A. , Thurston Herbert 
Published: August 2015

1. This study was designed to examine the effect of angiotensin-converting enzyme inhibitors on resistance artery structure and endothelium-dependent relaxation in Goldblatt two-kidney, one-clip hypertensive rats. Four weeks after clipping, hypertensive and sham rats were treated with either perindopril (1 mg day−1 kg−1) or quinapril (3 or 30mg day−1 kg−1). After 6 weeks mesenteric resistance arteries were mounted in a myograph for measurements of vascular structure. The endothelium-dependent relaxation response to acetylcholine and bradykinin and the response to the nitric oxide donor sodium nitroprusside were recorded.
2. All treatment regimes lowered the blood pressure and reversed both cardiac and resistance artery hypertrophy. Two-kidney, one-clip rats treated with quinapril showed a dose-dependent reduction in media cross-sectional area and media to lumen ratio.
3. Hypertension of 10 weeks' duration was associated with an impaired endothelium-dependent relaxation response to acetylcholine and bradykinin. Treatment with perindopril and either dose of quinapril prevented the development of impaired endothelium-dependent relaxation but had no effect on the response to sodium nitroprusside. Treatment had no effect on endothelium-dependent relaxation in sham rats.
4. Angiotensin-converting enzyme inhibitor treatment is effective in normalizing blood pressure and cardiovascular structural changes. Angiotensin-converting enzyme inhibitor treatment prevented the development of impaired endothelium-dependent relaxation to both acetylcholine and bradykinin. The ability of angiotensin-converting enzyme inhibitors to reverse cardiovascular structural changes and prevent the development of abnormal endothelium-dependent relaxation may contribute to the overall effect of this type of antihypertensive drug.
Bed Rest Decreases Whole-Body Protein Turnover in Post-Absorptive Man
Authors: Bettany G. E. A. , Ang B. C. , Georgiannos S. N. , Halliday D. , Powell-Tuck J. 
Published: August 2015

1. Whole-body protein turnover was measured using the [15N]glycine tracer technique in 10 post-absorptive healthy volunteers during normal daily activities and a period of bed rest.
2. Bed rest reduced whole-body protein turnover (25%), synthesis (26%) and breakdown (25%), but short-term urinary nitrogen excretion remained unchanged.
Unique Response of Human Arteries to Endothelin B Receptor Agonist and Antagonist
Authors: Liu James J. , Chen Joan R. , Buxton Brian F. 
Published: August 2015

1. The role of the ETB receptor in human arteries has not been well studied because of the lack of specific ETB receptor antagonists. In the present studies the specific ETB receptor antagonist BQ-788 and the specific ETB agonist IRL-1620 were used to characterize the function of the ETB receptor in human radial arteries and internal mammary arteries.
2. The results showed that the ETB antagonist BQ-788 significantly inhibited endothelin-1-induced contraction in internal mammary arteries, but not in radial arteries. In internal mammary arteries, BQ-788 at a concentration of 10 μmol/l shifted the endothelin-1-induced concentration-dependent curve to the right by one order. By comparison, the ETA receptor antagonist BQ-610 at 1 μmol/l produced a much more potent inhibitory effect (three-order shifting) on endothelin-1-induced contraction in internal mammary arteries, and also potently inhibited the contraction in radial arteries.
3. The ETB agonist IRL-1620 caused a contraction in internal mammary arteries, but not in radial arteries, although the response of radial arteries to endothelin-1 was very strong. The contraction induced by IRL-1620 was weaker than that induced by endothelin-1; however, the maximal contraction to IRL-1620 was obtained at 3 nmol/l, which was lower than that with endothelin-1 (maximal contraction at 10 nmol/l).
4. In internal mammary arteries the contraction to endothelin-1 and IRL-1620 gradually changed to relaxation with high concentrations of endothelin-1 (from 30 nmol/l) and IRL-1620 (from 3 nmol/l), whereas it did not in radial arteries; suggesting that the ETB receptor on human arterial smooth muscle cells may mediate contraction at low agonist concentrations and relaxation at high agonist concentrations.
5. The ETB agonist IRL-1620, endothelin-1 and endothelin-3 did not cause endothelium-dependent relaxation in either precontracted radial arteries or internal mammary arteries, although endothelium-dependent relaxation was fully induced by acetylcholine in these two arterial preparations.
6. In conclusion, the present studies demonstrate that the responses of internal mammary arteries and radial arteries to an ETB antagonist and an ETB agonist are significantly different from those of animal vascular vessels, and also from each other. The ETB receptor may play only a minor role in endothelium-dependent relaxation of these human arteries. Endothelin-1-induced contraction is mediated by both the ETA (major) and the ETB (minor) receptors in internal mammary arteries, but only by the ETA receptor in radial arteries. These studies may help to determine therapeutic strategy.