bluuebunny/crossref_metadata_2025_split huggingface dataset:
Lithium clearance measurements as an indication of cyclosporin a nephrotoxicity in the rat
Authors: Whiting P. H. , Simpson J. G. 
Published: August 2015

1. Measurements of the rate of lithium clearance, which provides an estimate of proximal renal tubular iso-osmotic reabsorption (i.e. sodium and H2O), were used to study H2O and electrolyte reabsorption during the development of cyclosporin A (CsA) induced nephrotoxicity.
2. CsA, administered daily by gavage at 50 mg/kg body weight, produced a nephrotoxicity which was characterized by reductions in the clearance rates of creatinine, sodium and potassium, and increased glycosuria, enzymuria and urine flow rate.
3. Decreased lithium clearance rate and increased proximal iso-osmotic reabsorption accompanied significant reductions in creatinine clearance rate. Absolute proximal tubular reabsorption, however, was not affected by CsA administration.
4. Reductions in the absolute distal tubular reabsorption of sodium, potassium and H2O were also observed.
5. Alterations in renal tubular function occur early in the development of CsA nephrotoxicity as a result of both direct proximal tubulotoxicity and an effect on the afferent arteriole.
6. Measurements of the rate of lithium clearance may be a useful adjunct to the diagnosis of CsA nephrotoxicity.
Selective alteration of brush-border hydrolases in intestinal diseases in childhood
Authors: Phillips A. D. , Smith M. W. , Walker-Smith J. A. 
Published: August 2015

1. Biochemical estimates of lactase, sucrase and maltase activities, carried out on intestinal biopsies appearing histologically normal, were compared with those obtained from children suffering from coeliac disease, cow's milk protein intolerance/postenteritis syndrome and the intractable diarrhoea syndrome of infancy. Lactase deficiency in these children was found to be more pronounced than sucrase or maltase deficiencies.
2. Quantitative cytochemical investigations showed characteristic disease-induced changes in the ability of enterocytes to express α- and β-glucosidases, but not alkaline phosphatase activities, during migration along stunted villi.
3. Separate estimates of the time course describing hydrolase development in normal and coeliac tissue showed the initial rate of lactase appearance to be halved in coeliac patients, while that for α-glucosidases remained constant and that for alkaline phosphatase increased by a factor of four. Enteroblastic replacement of mature enterocytes cannot provide a general explanation for hydrolase deficiency in diseased intestine.
Origins of endogenous noradrenaline overflow during reperfusion of the ischaemic rat heart
Authors: Dart A. M. , Riemersma R. A. 
Published: August 2015

1. Reperfusion of the globally ischaemic isolated rat heart is associated with an enhanced overflow of endogenous noradrenaline (NA) after ischaemic periods of 20, 40 or 60 min but not of 10 min.
2. Reperfusion NA overflow, after 40 min of ischaemia, is suppressed by desipramine and increased when ischaemia follows a period of substrate deprivation.
3. Reperfusion after 40 min of ischaemia is associated with a significant rise in NA concentration despite a simultaneous 20-fold increase in flow. This increase in concentration is abolished by treatment with desipramine or if ischaemia follows a period of substrate deprivation.
4. Reperfusion NA overflow correlates with the reperfusion overflow of an extracellular space marker infused before the ischaemic episode.
5. These results suggest that ischaemia is heterogeneous and that NA is released into regions of particularly profound ischaemia from which it is subsequently eluted during reperfusion.
A ouabain-displacing factor in normal pregnancy, pregnancy-induced hypertension and pre-eclampsia
Authors: Gregoire I. , Roth D. , Siegenthaler G. , Fievet P. , Esper N. El , Favre H. , Fournier A. 
Published: August 2015

1. A ouabain-displacing factor (ODF) was measured in the urine of non-pregnant, normotensive pregnant and hypertensive pregnant women by a receptor-binding assay with sodium, potassium-dependent adenosine triphosphatase.
2. Urinary ODF was significantly increased in normal pregnancy.
3. Greater increases were seen in pregnancy-induced hypertension and pre-eclampsia.
Effect of age and posture on human lymphocyte adenylate cyclase activity
Authors: Mader Scott L. , Robbins Alan S. , Rubenstein Laurence Z. , Tuck Michael L. , Scarpace Philip J. 
Published: August 2015

1. A number of age-related changes have been reported in the catecholamine–adrenoceptor–adenylate cyclase system. Most of the data available on these alterations come from resting subjects; the response to acute stress may provide additional insights into the age effect on these responses.
2. We measured supine and 10 min upright plasma noradrenaline and lymphocyte adenylate cyclase activity in ten healthy elderly subjects (age 66–80 years) and seven healthy young subjects (age 27–34 years).
3. Isoprenaline stimulation of lymphocyte adenylate cyclase activity was not significantly different between supine and upright positions or between elderly and young subjects. There was a marked increase in forskolin-stimulated adenylate cyclase activity in the upright posture in both elderly and young subjects. The increment over supine levels was 70% in the elderly (P &lt; 0.025) and 73% in the young (P &lt; 0.05). This enhanced forskolin activity was not seen in two young subjects who became syncopal.
4. These data suggest that enhanced forskolin-stimulated adenylate cyclase activity occurs after 10 min of upright posture in both elderly and young subjects, and may be relevant to immediate blood pressure regulation. We were unable to demonstrate any age-related differences in these acute adrenergic responses.
Effects of pH and osmolarity on aerosol-induced cough in normal volunteers
Authors: Lowry R. H. , Wood A. M. , Higenbottam T. W. 
Published: August 2015

1. The chemosensitivity of cough receptors stimulated by inhalation of aqueous aerosols was evaluated in 21 normal volunteers in three experiments.
2. The pH of isotonic saline was altered using small amounts of phosphate or glycine buffers to produce solutions with a pH range of 2.6–10.0. These solutions were nebulized ultrasonically and breathed for 1 min periods by seven subjects in random order and on separate days. Cough frequency during each 1 min inhalation was recorded. Only the two solutions of extreme pH (2.6 and 10.0) caused cough.
3. The effect of altering the osmolarity of the inhaled aerosol on cough was assessed using d-glucose over a range of 77–1232 mosmol/l. Saline solutions over the same range of osmolarity were also tested. The pH of d-glucose was raised to match that of saline by adding small amounts of sodium hydroxide. All solutions were nebulized and inhaled by seven subjects as described above for 1 min periods during which cough frequency was recorded. Forced expired volume in 1 s was recorded after each inhalation and did not alter in any subject by more than 10%. Subjects coughed when inhaling all the d-glucose solutions over the whole range of osmolarity. Cough occurred with saline solutions only at low chloride concentration and at the highest concentration.
4. In order to clarify whether the response to hypertonic saline was due to the high ionic content of the solutions or to its hypertonicity, two other solutions were tested. These were an isotonic and a hypertonic mixture of d-glucose and saline, containing ‘normal’ (150 mmol/l) ionic content. Cough occurred with the hypertonic solution but not with the isotonic solution, suggesting that hypertonicity does stimulate cough.
5. The mechanism of cough induction by citric acid was studied. An aerosol of 0.68% citric acid in saline was compared with sodium citrate, both with and without chloride, with d-glucose and with water in seven subjects. Cough occurred in response to all aerosols except sodium citrate in saline solvent. Additive effects of low pH and lack of chloride, and not the citrate ion, are responsible for the irritant properties of citric acid.
6. The chemosensitivity of the cough reflex induced by inhaled aerosols mirrors that already described in vivo for laryngeal rapidly adapting receptors.
Cyclosporin a prevents sensitization after blood transfusion in multiparous rats
Authors: Jones M. C. , Power D. A. , Stewart K. N. , Catto G. R. D. 
Published: August 2015

1. Humoral immune responses to allogeneic blood transfusions and semi-allogeneic pregnancies were monitored by the indirect haemagglutination assay in strains of inbred rats.
2. Similar titres and ranges of cross-reactive allo-antibodies were induced by blood transfusions and pregnancy; the maternal alloantibody response to paternal antigens was not increased by an unrelated antigenic stimulus.
3. Immunosuppression with cyclosporin, A was effective in preventing the primary humoral immune response produced by blood transfusion but not in abrogating the established immune response to previous pregnancy.
4. These studies have established an animal model of sensitization that both stimulates, the clinical situation of many potential renal transplant recipients and permits analyses of the different antigenic stimuli involved.
Increased levels of platelet-activating factor (1-O-alkyl-2-acetylglycerophosphocholine) in blood after reversal of renal clip hypertension in the rat
Authors: McGowan H. M. , Vandongen R. , Kelly L. D. , Hill K. J. 
Published: August 2015

1. This study analyses whole blood in acutely unclipped one-kidney, one-clip (1K,1C) hypertensive rats for the presence of platelet-activating factor (PAF), a potent vasodilator and a putative mediator of the rapid blood pressure (BP) fall seen after unclipping.
2. Hypertensive 1K,1C rats were anaesthetized and a carotid and jugular cannula were inserted for BP measurement and anaesthetic infusion respectively. After a stable level of anaesthesia was attained, the constrictive clip was removed and BP was recorded for 30 min.
3. Blood was drawn from the aorta directly into ice-cold acetone. The extract was analysed for PAF by a bioassay using 5-hydroxy-[14C]tryptamine-labelled platelets.
4. Rats which showed a BP fall had elevated levels of PAF [55 ± 6 (sem) pg/ml] when compared with those with no fall in BP [26 ± 7 (sem) pg/ml] (P &lt; 0.01).
5. This supports the hypothesis that activation of PAF biosynthesis may be a mechanism contributing to the fall in BP seen after unclipping the 1K,1C hypertensive rat.
Changes in jejunal permeability and passive permeation of sugars in intestinal biopsies in coeliac disease and Crohn's disease
Authors: Dawson D. J. , Lobley R. W. , Burrows P. C. , Notman J. A. , Mahon M. , Holmes R. 
Published: August 2015

1. The relative effects of changes in mucosal surface area and mucosal permeability on the passive uptakes of mannitol and raffinose have been studied in vitro using jejunal biopsies from 48 controls, 32 patients with coeliac disease and 11 patients with Crohn's disease. Total mucosal permeation was corrected for surface area measured morphometrically to provide an index of mucosal permeability.
2. In untreated coeliac disease, permeation of mannitol was reduced by 35% (P = 0.006) and that of raffinose was increased by 66% (P = 0.0095) compared with controls, whereas mucosal permeability to mannitol was increased twofold (P = 0.009) and to raffinose fivefold (P = 0.0001). Mucosal permeability was similar for each sugar.
3. In treated coeliac disease, permeation and permeability for mannitol were normal, but remained elevated for raffinose by 23% (P = 0.036) and 41% (P = 0.024), respectively.
4. In Crohn's disease, permeation of mannitol was reduced by 21%, but that of raffinose and mucosal permeability to both sugars were normal.
5. These findings suggest that surface area is quantitatively more important than mucosal permeability in determining the total permeation of mannitol, while the converse is true for raffinose. The findings are compatible with paracellular uptake of raffinose, but with both paracellular and transcellular uptake of mannitol. Both pathways are affected in coeliac disease, whereas only transcellular uptake is affected in Crohn's disease.
31P nuclear magnetic resonance study of steady-state adenosine 5′-triphosphate levels during graded hypoxia in the isolated perfused rat kidney
Authors: Ratcliffe P. J. , Endre Z. H. , Scheinman S. J. , Tange J. D. , Ledingham J. G. G. , Radda G. K. 
Published: August 2015

1. A model of controlled hypoxia in the isolated perfused rat kidney has been used to compare the extent of reduction in the steady-state level of adenosine 5′-triphosphate (ATP) from that initially observed with alterations in renal function and with the development of tubular cell injury.
2. ATP depletion was observed in response to decreased total oxygen delivery even when delivery greatly exceeded consumption and the venous oxygen tension remained in excess of 150 mmHg.
3. Increases in the fractional excretion of sodium occurred progressively below an apparent threshold value of whole kidney ATP of approximately 80% of the baseline.
4. With modestly decreased oxygen delivery, cellular injury was confined to deep proximal tubule and medullary thick ascending limb of Henle's loop. Severely decreased oxygen delivery rates were associated with cellular damage spreading throughout the cortex.
5. Even the smallest reductions in whole kidney ATP were associated with morphological damage to tubular cells. The extent of reduction in whole kidney ATP was closely correlated and approximately equivalent to the calculated volume of injured cells.
6. Our results indicate that reduction in whole kidney ATP during decreased oxygen delivery is a valid marker of the extent of injurious cellular hypoxia and are consistent with the view that cellular ATP concentrations in hypoxia are markedly inhomogeneous. They support the hypothesis that specific regions of the perfused kidney become critically hypoxic and develop cellular injury while overall oxygen delivery remains high. Areas at risk include deep proximal tubule as well as the medullary thick ascending limb of Henle's loop.
Dynamic measurement of human capillary blood pressure
Authors: Williams S. A. , Wasserman S. , Rawlinson D. W. , Kitney R. I. , Smaje L. H. , Tooke J. E. 
Published: August 2015

1. Capillary blood pressure was measured in man using a dynamic servo-nulling system and direct micropuncture. This enabled assessments of the normal variations in pressure which influence fluid filtration and reabsorption.
2. Seventy-eight capillaries in 19 subjects were punctured in one of three positions around the capillary loop with the hand at the level of the sternal angle. Mean pressure around the loop fell from 37.7 ± 3.7 mmHg (arteriolar limb, mean ± sem, n = 12) to 19.4 ± 1.0 mmHg (apex, n = 25) to 14.6 ± 0.5 mmHg (venular limb, n = 41) at skin temperatures of 18.7–33.1°C. These values agree closely with Landis' original studies in 1930 [E. Landis (1930) Heart, 15, 209–228].
3. The mean filtration/reabsorption state of any particular capillary limb was not static because of cardiac, vasomotor and respiratory fluctuations in capillary pressure. From a total of 38 capillaries in which recordings were analysed for 30 s, the fluctuations in pressure were such that 27 capillaries probably had periods of both filtration and reabsorption.
4. Computerized superimposition and coherent averaging of trains of capillary pulses enabled an accurate description of the pulse waveform to be made in three capillaries. This was remarkably similar to waveforms from the radial artery, albeit at reduced amplitude (average 3.6 ± 3.4 mmHg, mean ± sd overall). The time for the pulse to travel between the radial artery and the finger capillary was approximately 10 ms, which implies a propagation velocity of several metres per second.
5. Fourteen long recordings of capillary pressure (mean 154 s) were subjected to computerized Fourier analysis and cross-correlation with other parameters. Low frequency fluctuations between 0.02 and 0.2 Hz (0.086 ± 0.05 Hz, mean ± sd) correlated closely with vasomotion in simultaneously recorded (laser-Doppler) skin blood flow (0.080 ± 0.5 Hz), although they were not synchronous. Higher frequencies between 0.2 and 0.6 Hz (0.28 ± 0.03 Hz) correlated well with respiration (0.29 ± 0.03 Hz), were synchronous and probably relate to respiratory fluctuations in venous pressure. The dynamic system has thus enabled us to describe the considerable variations in normal capillary pressure and to relate this variability to physiological influences.
Atrial natriuretic peptide and catecholamines in peripheral blood as indicators of cardiac dysfunction in the general population
Authors: Caidahl Kenneth , Hedner Jan , Hedner Thomas 
Published: August 2015

1. From a screened cohort of 644 67-year-old men, drawn from the population of Gothenburg, 42 men with presumed cardiac dyspnoea were selected and compared with 45 random controls.
2. Cardiac function was evaluated by echocardiography and other non-invasive methods, and the potential of peripheral venous concentrations of immunoreactive atrial natriuretic peptide (IrANP), noradrenaline and adrenaline in revealing cardiac dysfunction was investigated.
3. Concentrations of venous IrANP and noradrenaline were both significantly, but weakly, related to the degree of dyspnoea and to pulmonary congestion.
4. IrANP, but not catecholamines, was also related to other indices of heart failure. The correlations were, however, due solely to increased immunoreactivity in men with severe dyspnoea; in most subjects with mild to moderate dyspnoea the level of IrANP was similar to that of the controls.
5. It is concluded that, in a population sample, the peripheral venous level of IrANP is more closely related to cardiac function than are catecholamines. Yet, the level of IrANP is not a very sensitive marker of cardiac dysfunction, suggesting that stimulation of α-human atrial natriuretic peptide release is a late phenomenon in the development of cardiac failure.
Diphosphonates and phosphate homoeostasis in man
Authors: McCloskey E. V. , Yates A. J. P. , Gray R. E. S. , Hamdy N. A. T. , Galloway J. , Kanis J. A. 
Published: August 2015

1. The effects of three intravenous diphosphonates (etidronate, clodronate and aminohexane diphosphonate) on phosphate homoeostasis were studied in 30 patients with Paget's disease of bone and in three patients with hypoparathyroidism.
2. In Paget's disease, all three diphosphonates induced significant increases in serum phosphate and renal tubular reabsorption of phosphate. This effect was most marked and persistent after etidronate, whereas in the clodronate- and aminohexane diphosphonate-treated patients the increases were less, of shorter duration and followed thereafter by significant decreases in serum phosphate and renal tubular reabsorption of phosphate. Unlike etidronate, both clodronate and aminohexane diphosphonate caused a significant reduction in serum and urinary calcium, with appropriate homoeostatic increases in immunoassayable parathyroid hormone.
3. Phosphaturic responses to infused parathyroid hormone were observed in two patients with etidronate-induced hyperphosphataemia.
4. In three hypoparathyroid patients, clodronate induced a more marked increase in serum phosphate and renal tubular reabsorption of phosphate than in Paget‘s disease, which was of comparable degree but of shorter duration than that after etidronate in Paget's disease.
5. These findings suggest that all three diphosphonates increase renal tubular reabsorption of phosphate, but that this effect is attenuated with those diphosphonates which induce secondary hyperparathyroidism.
Plasma alkaline phosphodiesterase I in intrahepatic cholestasis induced by α-naphthylisothiocyanate in rats
Authors: Quayle Julie A. , Capstick Alison , Morris Anthony I. , Billington David 
Published: August 2015

1. Administration of α-naphthylisothiocyanate (ANIT) to rats produced dose-dependent increases in plasma bile acid and bilirubin concentrations. Similar increases in plasma bile acid and bilirubin concentrations were evident in bile duct ligated rats, indicating that the severity of cholestasis is almost identical in both models.
2. Plasma alkaline phosphodiesterase I was increased by only 50–80% while alkaline phosphatase was increased more than threefold after ANIT administration. This is in contrast to an earlier study [S. R. Simpson, K. Rahman & D. Billington (1984) Clinical Science 67, 647–652] where, after bile duct ligation, serum alkaline phosphodiesterase I was elevated sixfold before any increase in alkaline phosphatase activity became apparent. Thus, plasma alkaline phosphodiesterase I does not offer as sensitive a marker of intrahepatic cholestasis (induced by ANIT) as it does of extrahepatic cholestasis (induced by bile duct ligation).
3. Hepatic alkaline phosphodiesterase I was unaffected by ANIT pretreatment while hepatic alkaline phosphatase was increased up to seven times. It is suggested that raised plasma alkaline phosphodiesterase I is due to regurgitation of the biliary enzyme rather than overspill of the enzyme from liver into blood.
4. Gel filtration showed that 24 h and 96 h after ANIT administration, rat serum contained a high molecular weight form of alkaline phosphodiesterase I, suggesting a different isoenzyme profile.
Interactions among stimulated human polymorphonuclear leucocytes, released elastase and bronchial antileucoprotease
Authors: Kramps J. A. , VanTwisk Ch. , Klasen E. C. , Dijkman J. H. 
Published: August 2015

1. We investigated the effect of stimulated human polymorphonuclear leucocytes (PMN's) on both the antitrypsin and anti-elastase activity of bronchial antileucoprotease (ALP).
2. Incubation of ALP with stimulated human PMN's resulted in a rapid loss of anti-elastase activity which paralleled that of the antitrypsin activity, suggesting that both inhibitor activities are represented by the same active site.
3. The myeloperoxidase-oxidizing system was found to be responsible for the inactivation of ALP.
4. The oxidized inhibitor was unable to form stable complexes with PMN elastase but was resistant to breakdown by proteolytic enzymes from stimulated PMN's.
5. It was observed that stimulated cells are capable of releasing elastase which shows full activity in the presence of a large molar excess of ALP.
6. We conclude from this study that stimulated PMN‘s are able to inactivate ALP by which released elastase is able to express enzymatic activity in spite of the presence of this low-molecular-weight inhibitor. Thus, inactivation of ALP by triggered PMN's may contribute to destructive processes in which elastase is thought to be a mediator.