bluuebunny/crossref_metadata_2025_split huggingface dataset:
Hepatic and Peripheral Insulin Action in Chronic Renal Failure before and during Continuous Ambulatory Peritoneal Dialysis
Authors: Heaton A. , Taylor R. , Johnston D. G. , Ward M. K. , Wilkinson R. , Alberti K. G. M. M. 
Published: August 2015

1. A three-step hyperinsulinaemic euglycaemic clamp was performed in six uraemic patients before dialysis and after 3 months of treatment with continuous ambulatory peritoneal dialysis, and in seven matched normal control subjects. Glucose turnover was assessed basally and during the clamp using [3-3H]glucose as a tracer.
2. The glucose infusion rate required to maintain euglycaemia was insignificantly higher in normal subjects compared with undialysed uraemic subjects at each insulin infusion rate.
3. The isotopically assessed total glucose turnover was also similar in normal and uraemic subjects. Basal hepatic glucose output was again similar in uraemic and control subjects and output was suppressed to a similar degree at each insulin infusion rate.
4. After treatment with continuous ambulatory peritoneal dialysis, the glucose infusion rate and the total glucose turnover during the clamp rose significantly at all three insulin concentrations (P &lt; 0.05), but remained insignificantly different from normal control values. Hepatic glucose output was unchanged.
5. Peripheral insulin action was improved during continuous ambulatory peritoneal dialysis, but hepatic insulin action was unchanged.
Atrial Natriuretic Factor Content of Brain Nuclei in Deoxycorticosterone Acetate-Salt Hypertension in the Rat
Authors: Geiger Helmut , Bahner Udo , Palkovits Miklos , Hupe Jürgen , Heidland August 
Published: August 2015

1. The influence of deoxycorticosterone acetate (DOCA)–salt hypertension on brain atrial natriuretic factor (ANF) in rats was investigated to elucidate the role of central ANF in a renin-independent model of experimental hypertension.
2. Sprague-Dawley rats were subjected to uninephrectomy and given either tap water or saline [1% (w/v) NaCl] to drink plus weekly injections of either saline or DOCA (25 mg/kg, subcutaneously). After 32 days, the rats were decapitated and 18 different brain nuclei were removed by a micropunch technique.
3. The systolic blood pressure of the DOCA-salt rats was significantly higher than that of control rats [154 ± 3 mmHg vs 104 ± 2 mmHg (20.53 ± 0.40 kPa vs 13.86 ± 0.27 kPa), P &lt; 0.001].
4. Plasma ANF levels were significantly (P &lt; 0.01) higher in DOCA-salt hypertensive rats compared with control rats.
5. In DOCA-salt hypertensive rats, the ANF content was increased in the organum vasculosum of the lamina terminalis (31.4 ± 2.1 vs 22.1 ± 2.5 pg/mg of protein, P &lt; 0.05), the subfornical organ (32.5 ± 5.0 vs 24.2 ± 2.4 pg/mg of protein, P &lt; 0.05), the medial amygdaloid nucleus (49.0 ± 6.4 vs 34.0 ± 2.0 pg/mg of protein, P &lt; 0.05) and the locus coeruleus (86.9 ± 4.1 vs 64.4 ± 4.2 pg/mg of protein, P &lt; 0.01) compared with control rats. The ANF content of 14 other brain areas investigated did not alter after treatment.
6. Our data demonstrate that the development of DOCA-salt hypertension in rats is associated with changes in the ANF content of specific brain areas, especially the locus coeruleus, and is consistent with an important pathophysiological role of this pontine area in the development of DOCA-salt hypertension.
Capillary Permeability and Extracellular Fluid Volumes in Pregnancy-Induced Hypertension
Authors: Brown Mark A. , Zammit Vivienne C. , Lowe Sandra A. 
Published: August 2015

1. Capillary permeability was determined by the disappearance rate of Evans Blue dye from plasma in healthy non-pregnant women, normal third-trimester primigravidae and primigravidae with pregnancy-induced hypertension
2. Extracellular fluid volume was determined from the disappearance curves of injected mannitol in the same subjects and the plasma volume was measured by the Evans Blue dye dilution technique
3. In normal pregnancy capillary permeability was not altered from that of non-pregnant subjects. Although extracellular fluid volume and plasma volume were increased in normal pregnant compared with nonpregnant women, the distribution of fluid between plasma volume and interstitial fluid volume was unaltered
4. Women with established pregnancy-induced hypertension had a more rapid Evans Blue disappearance rate and a lower plasma volume than normal pregnant women, independent of the presence of proteinuria. Maternal plasma volume correlated positively and significantly with fetal birth weight in women with pregnancy-induced hypertension, emphasizing the important relationship between maternal plasma volume and fetal outcome
5. The increased capillary permeability in women with pregnancy-induced hypertension was associated with a reduction in the plasma volume/interstitial fluid volume ratio but a normal extracellular fluid volume, suggesting that the reduced plasma volume did not result from sodium loss but rather from a redistribution of the total extracellular fluid volume. These changes did not differ significantly in subgroups with and without oedema.
Production of Methylguanidine in Dogs with Acute and Chronic Renal Failure
Authors: Brooks David P. , Rhodes Gerald R. , Woodward Paul , Boppana Venkata K. , Mallon Francine M. , Griffin H. Eugene , Kinter Lewis B. 
Published: August 2015

1. Methylguanidine is a suspected uraemic toxin that accumulates in renal failure
2. We measured methylguanidine in the plasma of dogs with acute ischaemic-induced renal failure and in the plasma and urine of dogs with spontaneous chronic renal insufficiency, using a highly sensitive method involving solid-phase extraction followed by h.p.l.c. with post-column fluorescence detection
3. Constriction of the remaining renal artery of four uninephrectomized dogs for 90 min resulted in a significant (P &lt; 0.01) increase in plasma creatinine concentration after 24 h (from 113 ± 3 to 303 ± 50 μmol/l; mean ± sem). Over the next 14 days, plasma creatinine fell towards baseline concentrations. Plasma methylguanidine also increased significantly (P &lt; 0.05) 24 h after renal occlusion (from 0.16 ± 0.04 to 0.86 ± 0.32 μmol/l) and showed a similar pattern to the plasma creatinine concentration
4. In a further four dogs, administration of mannitol (2 g/kg) at the time of reperfusion significantly attenuated these responses
5. Dogs with chronic renal failure demonstrated increased plasma concentrations and urinary excretion of methylguanidine, and the levels appeared to be related to the severity of renal insufficiency. Thus, the dogs with the highest plasma creatinine concentrations and lowest creatinine clearances had the highest plasma methylguanidine concentrations. The clearance of methylguanidine exceeded that of creatinine, indicating that the toxin undergoes renal tubular secretion.
Pulmonary Endothelium-Derived Relaxing Factor is Impaired in Hypoxia
Authors: Warren J. B. , Maltby N. H. , MacCormack D. , Barnes P. J. 
Published: August 2015

1. The vasoconstrictor and vasodilator activity of cultured bovine pulmonary artery endothelial cells was measured to determine how exposure to different partial pressures of O2 [Po2 142, 42 and 15 mmHg (18.9, 5.6 and 2 kPa)] affects the production of endothelial-derived relaxing and constrictor factors
2. A de-endothelialized rat aortic ring [maintained at a Po2 of 142 mmHg (18.9 kPa)] was used to bioassay the effluent from a perfused column of bovine endothelial cells grown on microcarrier beads. The endothelial cells were stimulated by 10−7 mol/l bradykinin given for 1 min at 12 min intervals
3. At the start, middle and end of the experiment the bovine endothelial cells were exposed to a Po2 of 142 mmHg (18.9 kPa) and when stimulated by bradykinin the perfusate caused respectively a 70 ± 4%, 63 ± 6% and 63 ± 6% (mean ± sem) relaxation of an aortic ring which had been pre-contracted by 10−6 mol/l phenylephrine. At a Po2 of 42 mmHg (5.6 kPa) the relaxation induced by the cells was not significantly altered, but this tailed to zero after 26–38 min exposure of the cells to a Po2 of 15 mmHg(2 kPa)
4. These responses were unaltered by the presence of 10−5 mol/l indomethacin, suggesting that prostacyclin is not a significant vasodilator in this system
5. Reduced production of endothelium-derived relaxant factor rather than production of a constrictor factor, or a direct effect on the smooth muscle, may be involved in pulmonary hypoxic vasoconstriction.
Monophasic action potential recordings in response to rapid transient elevation of extracellular potassium and their modification by β-adrenoceptor blockade in the anaesthetized dog
Authors: Sutton P. M. I. , Taggart P. , Swanton R. H. , Emanuel R. W. 
Published: August 2015

1. Monophasic action potentials (MAPs) were recorded simultaneously from the endocardium and the epicardium in open-chested dogs (n = 16) during bolus intravenous injections of potassium chloride at 0.1 mmol/kg and 0.2 mmol/kg. MAP duration was measured at 90% repolarization. Local conduction was measured as the delay between the pacing artefact and upstroke of the MAP.
2. The animals were anaesthetized with α-chloralose and urethane. Heart block was created by atrioventricular nodal ablation with 0.1% (v/v) formalin. Infra-nodal pacing was established.
3. Bolus injections of potassium chloride at 0.1 mmol/kg shortened MAP duration. The effect was maximal at 15 s after the injection [epicardium: 171.5 ± 3.0 (control) and 148.9 ± 5.2 ms at 15 s (P &lt; 0.001); endocardium: 178.7 ± 4.4 (control) and 165.6 ± 5.3 ms (P &lt; 0.001)]. The shortening on the epicardium was significantly greater than on the endocardium (P &lt; 0.05).
4. Local conduction time showed no significant change [epicardium: 37.8 ± 1.8 (control) and 41.2 ± 2.4 at 15 s; endocardium: 41.1 ± 1.6 (control) and 45.0 ± 3.4 at 15 s].
5. After β-adrenoceptor blockade, MAP duration shortened, exhibiting a maximum effect at 20 s after a bolus injection of potassium chloride at 0.1 mmol/kg [epicardium: 184.7 ± 7.1 (control) and 130.7 ± 9.0 ms at 20 s (P &lt; 0.001); endocardium 192.0 ± 7.4 (control) and 148.6 ± 10.8 ms at 20 s (P &lt; 0.001)]. The greater shortening observed on the epicardial surface did not reach statistical significance.
6. Local conduction time after β-adrenoceptor blockade was prolonged, reaching a maximum at 20 s [epicardium: 41.2 ± 4.8 (control) and 65.9 ± 8.6 ms at 20 s: endocardium: 47.5 ± 7.4 (control) and 87.3 ± 13.1 ms at 20 s].
7. Doubling of the dose of potassium chloride to 0.2 mmol/kg was usually terminal and often showed bizarre electrophysiological responses with striking regional differences.
8. Our results show that bolus injections of potassium chloride exert a differential influence on the time course of epicardial and endocardial repolarization by an effect on MAP duration rather than on local conduction time. After β-adrenoceptor blockade the effect of a bolus injection of potassium chloride on MAP duration was greater and conduction time was increased.
Alterations in β-adrenergic sensitivity and platelet α2-adrenoceptors in obese women: effect of exercise and caloric restriction
Authors: Berlin Ivan , Berlan Michel , Crespo-Laumonnier Brigitte , Landault Catherine , Payan Christine , Puech Alain J. , Turpin Gérard 
Published: August 2015

1. Peripheral adrenergic responses were studied in eight obese women before and after 15 days of caloric restriction (2500 kJ/day) and in eight sex- and age-matched lean controls.
2. β-Adrenergic sensitivity (defined as the dose of isoprenaline required to increase resting heart rate by 25 beats/min) was evaluated before and after the diet. Density and affinity (determined as the apparent dissociation constant) of platelet α2-adrenergic receptors, and plasma adrenaline and noradrenaline levels, were measured after overnight bed-rest and after 9 min of standardized exercise performed before and after the low caloric diet.
3. Before the diet basal antecubital venous plasma noradrenaline concentrations were lower in obese women when compared with lean women (0.94 ± 0.06 vs 1.27 ± 0.17 nmol/l, P &lt; 0.02). Isoprenaline sensitivity did not differ between lean and obese women.
4. At rest, platelet α2-adrenoceptor density was lower in overweight than in lean women (129 ± 21 vs 168 ± 16 fmol/mg of protein, P &lt; 0.02). Exercise significantly increased platelet α2-adrenoceptor density and decreased affinity in lean women. This decrease correlated with the rise in plasma noradrenaline.
5. In obese women exercise did not modify platelet α2-adrenoceptor density or affinity, despite a significant increase in plasma catecholamines. However, the increase in plasma noradrenaline during exercise was lower in obese women.
6. The low caloric diet produced a β-adrenergic supersensitivity.
7. We conclude that (a) obesity does not alter β-adrenergic sensitivity; (b) 15 days of caloric restriction produces a β-adrenergic supersensitive state; (c) obese women show an inability to desensitize platelet α2-adrenoceptors in response to exercise.
Biphasic response to acetylcholine in human veins in vivo: the role of the endothelium
Authors: Collier Joe , Vallance Patrick 
Published: August 2015

1. The dose-response to acetylcholine has been examined in dorsal hand veins of healthy volunteers before and after removal of the endothelium.
2. Measurements were made in single dorsal hand veins during local infusions of acetylcholine. The vein was irrigated with distilled water to remove the endothelium. Dilator studies were performed in vessels preconstricted by a continuous infusion of noradrenaline.
3. In the endothelium-intact vessel the dose-response to acetylcholine was biphasic; low doses produced venodilatation with higher doses causing venoconstriction.
4. Dilatation to low doses of acetylcholine was abolished by prior irrigation with distilled water, consistent with denudation of the endothelium by this process. Irrigation augmented the constriction seen in response to higher doses of acetylcholine.
5. This is the first demonstration of an endothelium-dependent biphasic dose-response to acetylcholine in man. The results raise questions as to the possible physiological actions of endogenous acetylcholine and as to the use of the acetylcholine dose-response curve as a marker of endothelial function.
Ethanol predominantly alters sodium influx in human leucocytes
Authors: Main J. , Thomas T. 
Published: August 2015

1. Although ethanol appears to alter cellular sodium transport, the exact nature of its effects has not been clearly defined. We have studied the effects of different concentrations of ethanol on human leucocyte sodium content, and on the rise in leucocyte sodium content which occurs during sodium pump blockade with ouabain.
2. Sodium content was significantly reduced after a 20 min incubation with ethanol at concentrations between 17 and 170 mmol/l.
3. The rise in sodium content during a 20 min incubation with ouabain was significantly less in the presence of 170 mmol/l ethanol as compared with 17 mmol/l ethanol.
4. These results suggest that the effect of ethanol on intracellular sodium content is independent of sodium pump activity, i.e. it is mediated through reduced sodium influx.
Severe metabolic acidosis and disturbances of calcium metabolism induced by acetazolamide in patients on haemodialysis
Authors: De Marchi Sergio , Cecchin Emanuela 
Published: August 2015

1. To investigate mechanisms of extrarenal buffering in uraemic acidosis, we studied the effects of the carbonic anhydrase inhibitor, acetazolamide, in normal subjects and in patients with end-stage kidney disease on maintenance haemodialysis with virtually no urine output.
2. Acetazolamide (500 mg) was administered daily for 7 days, after pretreatment for 1 month with 1,25-dihydroxyvitamin D (n = 12) or placebo (n = 12); only placebo was administered to a third group (n = 12) of haemodialysis patients. In addition, acetazolamide was administered to normal control subjects (n = 12).
3. Treatment with acetazolamide resulted in a more marked metabolic acidosis in haemodialysis patients than in normal control subjects and the effect in haemodialysis patients was attenuated by prior treatment with 1,25-dihydroxyvitamin D.
4. The administration of acetazolamide to haemodialysis patients led to an increase in serum inorganic phosphorus, bone isoenzyme of alkaline phosphatase and parathyroid hormone, and a reduction in serum calcium, whereas acetazolamide had no effect on these variables in normal subjects. In contrast, in the haemodialysis patients previously treated with 1,25-dihydroxyvitamin D, acetazolamide increased serum inorganic phosphorus, bone isoenzyme of alkaline phosphatase, parathyroid hormone and serum calcium.
5. We hypothesize that the metabolic acidosis induced by acetazolamide in haemodialysis patients may result from interference with the mechanisms of extrarenal buffering.
6. As parathyroid hormone, 1,25-dihydroxyvitamin D and carbonic anhydrase are thought to be involved in bone buffering, we suggest that the marked acidosis seen in haemodialysis patients treated with acetazolamide may be due to impaired parathyroid hormone-mediated bone buffering.
myo-Inositol influx into human leucocytes: methods of measurement and the effect of glucose
Authors: Simmons D. , Bomford J. , Ng L. L. 
Published: August 2015

1. Low intracellular concentrations of myo-inositol in diabetic cells may contribute to the development of tissue damage. The cause of these low levels is unknown, but inhibition of a putative myo-inositol transporter by high concentrations of glucose has been proposed. We have developed a triple-isotope method for estimating myo-inositol influx into human leucocytes and so investigated both the kinetics of this uptake in normal volunteers and the effect of glucose upon it.
2. Uptake was composed of a passive component with a rate constant of 2.4 ± 0.3 × 10−2 min−1 and a saturable component with a Km of 61 ± 23 μmol/l and a Vmax. of 11.3 ± 4.5 × 10−4 mmol min−1 l−1. Ouabain and low extracellular concentrations of sodium partly inhibited influx. Uptake was predominantly into the cytosolic fraction of the cell with 12% entering the membrane-associated fraction at both 5 and 10 min.
3. myo-inositol influx was significantly inhibited by both d- and l-glucose but not by sucrose. Neither cytochalasin B nor ethyl isopropyl amiloride significantly inhibited uptake.
4. It is concluded that a myo-inositol transporter exists in human leucocytes which is similar to that found in other species and tissues. Our technique allows myoinositol influx in diabetic subjects to be related to varying glycaemic control and tissue damage.
Genes encoding the β-chains of HLA-DR7 and HLA-DQw2 define major susceptibility determinants for idiopathic nephrotic syndrome
Authors: Clark A. Godfrey B. , Vaughan Robert W. , Stephens Henry A. F. , Chantler Cyril , Williams D. Gwyn , Welsh Kenneth I. 
Published: August 2015

1. We have investigated the frequencies of the major histocompatibility complex class II alleles by restriction fragment length polymorphism analysis, using DR, DQ and DP complementary DNA probes, in 40 Caucasoid steroid-sensitive nephrotic children.
2. A significant association with HLA-DR7 was demonstrated (P = 2 × 10−5; aetiological fraction 0.6). The DQB1 gene of HLA-DQw2 was present in 83% of our patients (P = 2 × 10−4; aetiological fraction 0.7). We present evidence that it contributes a second susceptibility allele.
3. A weak association between the uncommon HLA-DP-Cp63 allele and the disease was also observed.
4. Our data suggest that the immune events in steroid-sensitive nephrotic syndrome are defined by a particular immunogenetic background involving the β-chain genes of HLA-DR7 and HLA-DQw2.
Elevated expression of heat-shock protein gene in the fibroblasts of patients with scleroderma
Authors: Deguchi Yasuhiro , Kishimoto Susumu 
Published: August 2015

1. Scleroderma is a systemic autoimmune disorder characterized by fibrosis affecting the skin, lung, kidney and other organs. The 70 kDa heat-shock protein has been implicated as essential for cell function during cell growth and differentiation. To study the molecular basis of intracellular events in sclerotic fibroblasts, we compared the expression of the hsp 70 gene in sclerotic and normal control fibroblasts by a run on nuclear transcription assay and a Northern blot assay.
2. In the run on nuclear transcription assay, sclerotic fibroblasts expressed an approximately eightfold higher level of hsp 70 transcription than normal fibroblasts in the quiescent condition after serum starvation. After stimulation with serum, the transcription level of the hsp 70 gene was almost similar in sclerotic and normal control fibroblasts.
3. In the Northern blot assay, the hsp 70 gene transcript, which was present in increased amounts in sclerotic fibroblasts, exhibited normal size.
Transcutaneous electrical stimulation applied to the infratrochlear nerve induces a homatropine-resistant miosis in humans
Authors: Fusco B. M. , Alessandri M. , Campagnolo V. , Fanciullacci M. 
Published: August 2015

1. Both high- and low-intensity transcutaneous electrical stimuli were applied to the emergence of the infratrochlear nerve in 18 healthy subjects. The effect on the size of the homolateral pupil was investigated. The width of the pupil was also measured when high-intensity transcutaneous electrical stimulation was applied to the contralateral side.
2. The high-intensity pulse resulted in constriction of the pupil when the stimulation was homolateral. The miosis was slow in onset (120 s latency) and long-lasting (80 s). No pupillary changes were detected after either ipsilateral low-intensity or contralateral high-intensity stimuli.
3. In 11 healthy subjects, the pupillary response to transcutaneous electrical stimulation was evaluated during iris parasympathetic blockade induced by homatropine eyedrops. The disappearance of the light reflex due to homatropine was considered an index of the parasympathetic blockade. Afterwards, a high-intensity pulse was transcutaneously delivered to the emergence of the infratrochlear nerve and the ipsilateral pupil size was measured.
4. A reduction in the pupillary size followed the electrical stimulation, still under the effect of homatropine which abolished the light reflex. The time course of this pupillary constriction was similar to that seen without the influence of homatropine.
5. The findings suggest that homolateral miosis, observed after unilateral high-intensity stimulation of the infratrochlear nerve, does not stem from cholinergic activation. It has been suggested that miosis induced by transcutaneous electrical stimulation may be due to an antidromic activation of the iris sensory fibres.