bluuebunny/crossref_metadata_2025_split huggingface dataset:
Differential effects of sulindac and indomethacin on blood pressure in treated essential hypertensive subjects
Authors: Puddey I. B. , Beilin L. J. , Vandongen R. , Banks R. , Rouse I. 
Published: August 2015

1. Attenuation of the effectiveness of antihypertensive therapy by non-steroidal antiinflammatory (NSAI) drugs has been attributed to inhibition of systemic or renal vasodilator prostaglandin synthesis, or a combination of both.
2. Indomethacin is a NSAI drug with both renal and extrarenal cyclo-oxygenase inhibition properties. Sulindac is a relatively selective cyclooxygenase inhibitor said not to affect urinary prostaglandin excretion.
3. This study examines the relative effect on blood pressure of 4 weeks' treatment, with indomethacin 25 mg three times daily and sulindac 200 mg twice daily, in a randomized placebo controlled trial in 26 hypertensive subjects.
4. In nine patients treated with indomethacin, supine blood pressure rose 11 mmHg systolic and 4 mmHg diastolic by the end of the first week, whereas nine subjects treated with sulindac showed a fall in blood pressure similar to the trend seen in placebo-treated subjects.
5. Indomethacin treatment inhibited renal cyclo-oxygenase with a 78% reduction in urinary prostaglandin E2 excretion and 89% suppression of plasma renin activity. Neither measurement was affected by sulindac. Extrarenal cyclo-oxygenase activity was inhibited by both indomethacin and sulindac with serum thromboxane B2 decreasing by 96% and 69% respectively.
6. The results suggest that the pressor effect of NSAI drugs is predominantly related to renal cyclo-oxygenase inhibition. The lack of effect of sulindac on blood pressure may make it a safer therapeutic option if NSAI drug therapy is necessary in the hypertensive patient.
Phosphate metabolism in erythrocytes of critically ill patients
Authors: Bevington A. , Asbury A. J. , Preston C. J. , Russell R. G. G. 
Published: August 2015

1. Orthophosphate (Pi), adenosine 5′-diphosphate (ADP), adenosine 5′-triphosphate (ATP) and 2,3-diphosphoglycerate (2,3-DPG) were measured in the erythrocytes of patients in an intensive care unit.
2. The patients’ plasma concentration of Pi varied from 0.1 to 4.2 mmol/l, and the corresponding concentration in erythrocytes varied from 0.1 to 2.0 mmol/litre of cells.
3. Marked ATP depletion (less than 1 mmol/litre of cells) was only observed when erythrocyte Pi was less than 0.3 mmol/litre of cells and plasma Pi was less than 0.35 mmol/l. No dependence of 2,3-DPG concentration on the cellular concentration of Pi was detected.
4. The phosphorylation potential [ATP]/([ADP] × [Pi]) varied inversely with the erythrocyte concentration of Pi. Hence the calculated free energy of hydrolysis of ATP in the cell increased from −58 kJ/mol in the most hypophosphataemic samples to −51 kJ/mol in the most hyperphosphataemic. Such changes may adversely affect cell function by altering the steady state mass-action ratios of ATPase reactions.
5. When erythrocytes from normal donors were incubated in solutions containing 1 or 5 mmol/l Pi, the cellular concentrations of Pi stabilized at 1.09 and 2.85 mmol/litre of cells respectively. The corresponding rates of lactate production were 2.09 and 3.11 mmol h−1 litre−1 of cells.
6. In spite of this stimulation of glycolysis (and hence of the flux through ATP synthesizing steps of the Embden-Meyerhof pathway), no significant change in ATP concentration was observed. As in the patients' cells, this indicates that, when extracellular Pi concentrations are perturbed, the concentrations, in erythrocytes, of organic phosphates are more closely regulated than the concentration of Pi.
(Na+, K+)-ATPase regulation and NaCl intake: effects on circulating inhibitor and sensitivity to noradrenaline
Authors: Swann Alan C. 
Published: August 2015

1. These experiments examined the effects of a high NaCl diet on (Na+, K+)-ATPase in kidney, heart and cerebral cortex, on the level of circulating inhibitor of (Na+, K+)-ATPase in plasma, and on stimulation of (Na+, K+)-ATPase by treatment with dextro (d)-amphetamine.
2. High salt diet increased indices of (Na+, K+)-ATPase activity (K+-activated p-nitrophenylphosphatase activity and ouabain binding) in kidney medulla, prevented stimulation by amphetamine in cerebral cortex and reduced amphetamine stimulation in heart.
3. High NaCl feeding increased the plasma level of circulating inhibitor of (Na+, K+)-ATPase.
4. Amphetamine alone had no effect on inhibitor level but amphetamine administration reduced the increase in inhibitor with high NaCl feeding.
Effects of physiological concentrations of vasopressin on haemostatic function in man
Authors: Grant P. J. , Davies J. A. , Tate G. M. , Boothby M. , Prentice C. R. M. 
Published: August 2015

1. Plasma concentrations of vasopressin (aVP) attained under conditions of stress were simulated by infusing four volunteers with 0.25, 0.5, 1.0 and 2.0 pressor units of aVP over 1 h (units/h). Three subjects had all four infusions and one received only 1.0 unit/h.
2. Blood samples were taken for assay of factor VIII coagulant activity (FVIIIC), factor VIII related antigen (FVIIIRAg), the ristocetin cofactor (FVIIIRiCof), euglobulin lysis time (ELT) and aVP concentrations before infusion (time 0) and every 20 min for 80 min. Fibrinopeptide A (FPA) generation time was measured at time 0, 60 and 80 min.
3. At infusion rates of 0.25 unit/h median aVP levels peaked at 6.5 pg/ml and there was no change in haemostatic function. At 0.5 unit/h aVP levels peaked at 16.0 pg/ml, there was no change in FVIII or FPA generation time, and plasminogen activator activity (106/ELT2) rose from 100 to 400 units. At 1.0 unit/h, aVP levels rose to 25.4 pg/ml, FVIIIC rose by 160% and activator activity from 87 to 360 units. At 2.0 units/h, aVP concentrations reached 83 pg/ml, there was an increase in all modalities of FVIII and activator activity rose from 251 to 452 units. FPA generation time shortened and circulating plasma levels of FPA were increased.
4. There was a highly significant correlation between the percentage increases in all three components of FVIII and plasma aVP levels (FVIIIC: r = 0.87, P &lt; 0.0001; FVIIIRAg: r = 0.61, P &lt; 0.0001; FVIIIRiCof: r = 0.80, P &lt; 0.0001) and between the increase in plasminogen activator activity and aVP levels (r = 0.56, P &lt; 0.0001).
5. The results indicate that plasma concentrations of aVP comparable with those attained during stress cause a rise in FVIII, an increase in plasma activator activity and effects on FPA generation consistent with low-level activation of the coagulation mechanism. Endogenous vasopressin could mediate alterations in haemostatic function known to accompany events such as surgical operations.
Activities and subcellular distributions of hepatic lipases in control subjects and in patients with alcoholic fatty liver
Authors: Leung Nancy N. Y. , Cairns Stuart R. , Peters Timothy J. 
Published: August 2015

1. Human hepatic lipase activities were studied in needle biopsy specimens by fluorogenic and radioisotopic assay methods. Using analytical subcellular fractionation by sucrose density gradient centrifugation a lysosomal acid lipase, with pH optimum of 4.0, and an endoplasmic reticulum alkaline lipase, with pH optimum of 8.5, were demonstrated with the fluorogenic assay.
2. The apparent Km of the acid lipase was 17 μmol/l by the fluorogenic method and 23 mmol/l by the radioisotopic method. The values for alkaline lipase were 94 μmol/l and 1.4 mmol/l respectively.
3. Assay of these activities in biopsies from 16 control subjects and 42 chronic alcoholics showed increasing activity with increasing hepatic fatty infiltration when the fluorogenic assay was used: no differences were demonstrated with radioisotopic assay. These results suggest that depressed lipolysis due to a relative deficiency of triglyceride lipase is not a causal factor in triglyceride accumulation in chronic alcoholic fatty liver.
Vitamin D-dependent rickets type I in pigs
Authors: Fox John , Maunder Eleni M. W. , Randall Valerie A. , Care Anthony D. 
Published: August 2015

1. We have bred a strain of pigs with an inherited condition of hypocalcaemic rickets, transmitted by an autosomal-recessive mechanism.
2. Homozygous (affected) piglets grew at half the rate of their heterozygous (clinically normal) littermates, and developed profound hypocalcaemia with severe secondary hyperparathyroidism and hypophosphataemia by 8 weeks of age.
3. In the hypocalcaemic piglets, plasma 1,25-dihydroxyvitamin D levels were low or undetectable, and 24,25-dihydroxyvitamin D3 levels were also reduced despite 25-hydroxyvitamin D3 levels being 2-fold higher.
4. There was no detectable 25-hydroxyvitamin D3-1- or -24-hydroxylase enzyme activity in renal homogenates prepared from affected animals.
5. Plasma and intestinal calcium-binding protein levels were reduced in the hypocalcaemic piglets.
6. Sucrose density gradient analysis of intestinal cytosol, prepared in high-salt buffer, revealed the presence of a similar amount of a specific &lt;4.2S 1,25-dihydroxyvitamin D3 binder in both groups of piglets.
7. Administration of pharmacological doses of vitamin D3 to affected animals reversed the hypocalcaemia.
8. We conclude that this strain of pigs has vitamin D-dependent rickets type I.
Metabolism of vitamin D in patients with primary biliary cirrhosis and alcoholic liver disease
Authors: Mawer E. Barbara , Klass H. J. , Warnes T. W. , Berry Jacqueline L. 
Published: August 2015

1. The metabolism of isotopically labelled vitamin D2 and D3 has been investigated in eight patients with primary biliary cirrhosis and in five controls. The concentration of labelled vitamin D2 was lower than that of vitamin D3 in serum of patients with primary biliary cirrhosis on days 1 and 2 after intravenous injection (P &lt; 0.005 and P &lt; 0.05, respectively) but no difference was seen in controls.
2. Similar amounts of labelled 25-hydroxyvitamin D2 and D3 were seen in serum of the control group; the same pattern was observed in the primary biliary cirrhosis group, and no significant differences were observed between the two groups.
3. In both control and primary biliary cirrhosis groups, the serum concentration of labelled 24,25-dihydroxyvitamin D2 exceeded that of 24,25-dihydroxyvitamin D3 (significant for controls on day 2, P &lt; 0.02) but concentrations in the two groups were not different.
4. Concentrations of labelled 25,26-dihydroxyvitamin D3 were significantly higher than those of 25,26-dihydroxyvitamin D2 in the primary biliary cirrhosis group at all times and in the control group on days 2 and 3. Both 25,26-dihydroxyvitamin D2 and D3 were higher in the serum of patients with primary biliary cirrhosis than in controls (significant on day 1, P &lt; 0.05).
5. Urinary excretion over days 0–3 of radioactivity from both vitamins D2 and D3 was significantly higher in the primary biliary cirrhosis group than in controls: 12.03 vs 1.80% for vitamin D2 and 8.98 vs 1.76% for vitamin D3(P &lt; 0.005). Vitamin D2-derived urinary radioactivity in primary biliary cirrhosis correlated strongly with serum bilirubin (P = 0.005).
6. The metabolism of labelled vitamin D3 was studied in seven patients with alcoholic liver disease, three of whom showed low serum concentrations of labelled 25-hydroxyvitamin D3 suggesting impaired hepatic synthesis. The 25-hydroxylation response was quantified as the relative index of 25-hydroxylation and was significantly related to two other indices of liver function. It is concluded that impaired 25-hydroxylation of vitamin D may occur in alcoholic liver disease and results from hepatocellular dysfunction.
7. Less than the predicted amounts of 1,25-dihydroxyvitamin D3 were produced in four of the seven patients with alcoholic liver disease; this defect may be attributable in part to decreased precursor 25-hydroxyvitamin D and to poor renal function.
Sex differences in the hepatic uptake of sulphobromophthalein in the rat
Authors: Orzes N. , Bellentani S. , Aldini R. , Simoni P. , Ferretti I. , Lunazzi G. C. , Sottocasa G. L. , Tiribelli C. 
Published: August 2015

1. Sex difference in the hepatic uptake of sulphobromophthalein (BSP) was investigated in male and female rats in three different experimental models.
2. In the intact animal the BSP plasma disappearance rate was significantly higher (P &lt; 0.01) in females than in males when 0.15 or 1.5 μmol/kg body wt. was injected. Comparable values were found at the highest BSP dose (15 μmol/kg body wt.) used.
3. In the perfused liver, the first-pass hepatic extraction and the uptake velocity were significantly higher (P &lt; 0.001) in female rats at low BSP doses (0.3–750 μmol/g of liver) whereas identical values were found at higher concentrations.
4. In hepatocytes isolated by collagenase perfusion, the BSP uptake occurs via two different uptake sites in both sexes. The Km of the high affinity sites was lower in females than in males (3.67 ± 0.58 vs 7.24±0.68 Mmol/l, P &lt; 0.001) whereas Vmax. showed comparable values (2.70 ± 0.36 vs 2.47 ± 0.45 nmol of BSP/mg of protein, NS). In contrast, no difference was found in the kinetic parameters of the low affinity sites (Km 50.6±31.1 vs 61.0±17.5 μmol/l; Vmax. 21.9 ± 13.2 vs 25.0±3.6 nmol of BSP/mg of protein, mean ± sd, NS, females and males respectively).
5. Taken together these data show that low doses of BSP are taken up by the liver more efficiently in female than in male rats and are consistent with a sex-related difference in the affinity but not in the number of the BSP high affinity uptake sites.
Breathlessness during different forms of ventilatory stimulation: a study of mechanisms in normal subjects and respiratory patients
Authors: Adams L. , Lane R. , Shea S. A. , Cockcroft A. , Guz A. 
Published: August 2015

1. This study investigates the mechanisms underlying the perception of breathlessness induced by hypoxia and hypercapnia in both naive normal subjects and patients with respiratory mechanical problems.
2. In normal subjects separately receiving both oscillating hypercapnic and hypoxic ventilatory stimulation, equivalent peak stimulus intensities in end-tidal gas were associated with a ‘damped’ ventilatory response when the frequency of stimulation was increased. A concomitant fall in peak breathlessness levels on a visual analogue scale was recorded in each case.
3. In normal subjects and patients, the voluntary copying of a ventilatory pattern recorded during oscillating hypercapnic stimulation was associated with a marked diminution or complete absence of breathlessness despite equivalent levels of peak ventilations achieved.
4. Voluntary copying of hypercapnic stimulated ventilation was not associated with any demonstrable change in the distribution of muscle movements between the chest wall and abdomen.
5. These results suggest that the intensity of breathlessness depends on the level of effective reflex stimulation of the respiratory-related neurones in the medulla. They cannot be explained solely in terms of perception of afferent neural information arising from either chemoreceptors or respiratory mechanoreceptors.
Evaluation of glycerol as an osmotic agent for continuous ambulatory peritoneal dialysis in end-stage renal failure
Authors: Heaton A. , Ward M. K. , Johnston D. G. , Alberti K. G. M. M. , Kerr D. N. S. 
Published: August 2015

1. Six patients established on continuous ambulatory peritoneal dialysis entered a trial of treatment with dialysis fluid containing glycerol instead of glucose as the osmotic agent in an attempt to decrease the energy load. They were observed for a further 6 months after reconversion to glucose-based dialysis.
2. During the 6 month control period fluid balance was achieved mainly with a solution containing 76 mmol of glucose/l. Fluid balance was maintained during the 6 month period of treatment with glycerol only by the increased use of solutions containing a high concentration of glycerol (152 mmol/l and 272 mmol/l). Thus the energy value of the absorbed osmotic agent did not differ at a mean of 1607 kJ (384 kcal)/day using glycerol and 1669 kJ (399 kcal)/day using glucose as the osmotic agent.
3. In five subjects, fasting and peak blood glycerol levels did not change over the 6 months, but one subject, who accumulated glycerol, developed symptoms of hyperosmolality after 2 months and glycerol therapy was discontinued. In a further subject glycerol-based dialysis was terminated at 3 months when increasing angina was reported.
4. Mean fasting plasma triglyceride concentrations were 50% higher during the 6 months on glycerol (3.12 ± 1.12 mmol/l) than on glucose (2.19 ± 0.97 mmol/l) (P &lt; 0.05). There was a small rise in very low density lipoprotein-cholesterol concentrations with glycerol dialysis but total cholesterol levels were unchanged.
5. The absorption of glycerol was not associated with an acute rise in circulating glucose or insulin but the mean blood glucose, over a 6 h dialysis cycle, had risen by 0.5 mmol/l after 3 months' treatment with glycerol and the mean serum insulin had risen from 5.9 ± 0.7 m-units/l to 9.8 ± 0.6 m-units/l (P &lt; 0.01).
6. This study demonstrated no substantial advantage of glycerol over glucose as an osmotic agent in non-diabetic patients on continuous ambulatory peritoneal dialysis.
Abnormalities of peripheral venous tone in women with pregnancy-induced hypertension
Authors: Stainer Karen , Morrison Rachel , Pickles C. , Cowley A. J. 
Published: August 2015

1. Forearm venous tone was measured in two groups of pregnant women: one group with pregnancy-induced hypertension and the other group with normal blood pressure.
2. The women with pregnancy-induced hypertension were venoconstricted in the forearm (P &lt; 0.01) compared with the pregnant women with normal blood pressure. However, there was no difference in venous tone between the women with pregnancy-induced hypertension and nonpregnant women.
3. There was an inverse correlation between mean arterial blood pressure and forearm venous tone (r = −0.581, P &lt; 0.001) for all the pregnant women studied. Further evaluation of peripheral venous tone may provide valuable information about the pathophysiology and treatment of women with pregnancy-induced hypertension.
Antihypertensive effects of S9490-3, a new converting enzyme inhibitor, in the conscious spontaneously hypertensive rat
Authors: Barres C. , Cerutti C. , Paultre C. Z. , Sassard J. 
Published: August 2015

1. The acute and chronic cardiovascular effects of S9490-3, a new converting enzyme inhibitor, were studied by means of a computerized analysis of the intra-aortic blood pressure recorded for 48 consecutive hours, in the conscious, unrestrained adult spontaneously hypertensive rat (SHR). The software used allowed the simultaneous study of one control and one treated animal.
2. A single intravenous dose of S9490-3 (2 mg/kg) induced a rapid fall in systolic and diastolic blood pressure, which remained significant for 11 h. This decrease was not associated with an elevation in heart rate.
3. A chronic oral treatment with S9490-3 (1 mg/kg/24h for 12 days) significantly lowered systolic and diastolic blood pressure and reduced the variability of systolic blood pressure. The heart rate was slightly increased at rest (day time) but significantly elevated in the freely exercising SHR (night time). However, it must be noted that this increase remained moderate.
4. The baroreflex sensitivity of chronically treated animals was enhanced when measured after phenylephrine but not after nitroglycerine bolus.
5. Chronically given S9490-3 significantly reduced the pressor effect of phenylephrine and decreased the left ventricle weight.
Cardiovascular and metabolic responses to low dose adrenaline infusion: an invasive study in humans
Authors: Freyschuss U. , Hjemdahl P. , Juhlin-Dannfelt A. , Linde B. 
Published: August 2015

1. Cardiovascular and metabolic responses to intravenous infusions of adrenaline (ADR), which raised arterial plasma ADR in a stepwise fashion from 0.3 to 1.3, 2.3 and 6.0 nmol/l, were studied in 11 healthy volunteers.
2. ADR evoked marked and concentration-dependent increases in stroke volume and cardiac output (thermodilution), as well as decreases in the vascular resistances of the systemic circulation, calf and adipose tissue. These changes were significant from 1.3 nmol/l ADR. Less marked effects were found on blood pressure and heart rate.
3. Significant arterial ADR concentration-effect relationships were found for cyclic AMP, glycerol, glucose, lactate and noradrenaline, but not for insulin. Cyclic AMP and glycerol were significantly elevated at 1.3, glucose at 2.3, but lactate not below 6.0 nmol/l ADR. Increases in adipose tissue blood flow and arterial glycerol levels were correlated (P &lt; 0.001), suggesting a metabolic component in the blood flow response of adipose tissue.
4. Invasive haemodynamic measurements revealed that ADR at arterial concentrations within the lower physiological range had considerable effects on cardiac output and vascular resistances, despite moderate changes in the conventional non-invasive haemodynamic variables blood pressure and heart rate.
5. ADR elicited clear-cut responses at arterial plasma concentrations attained during various kinds of mild to moderate stress.
Diffusion of butyrate through pig colonic mucus in vitro
Authors: Smith Gavin W. , Wiggins Philippa M. , Lee Sum P. , Tasman-Jones Clifford 
Published: August 2015

1. Using a modified equilibrium dialysis cell the rate of diffusion of butyrate through pig colonic mucus has been compared with that through other gels and unstirred layers.
2. Relative diffusion coefficients were calculated for each layer. Layers of 8% polyacrylamide, and of caecal, mid-colonic and terminal colonic mucus, had coefficients that were 50–60% of the apparent free diffusion coefficient for butyrate, determined using layers made up of Millipore filters alone.
3. The apparent free diffusion coefficients for butyrate (layers of agarose or filters) were 70% of previously determined values in the literature. This discrepancy can be explained by elements of the experimental procedure.
4. All mucus layers differed significantly from layers of 2% agarose and Millipore filters but were not significantly different from layers of 8% polyacrylamide or from each other.
5. Diffusion coefficients for butyrate in the mucus samples correlated with water content and carbohydrate content but had no relationship to protein content.
6. The rate of diffusion of butyrate in colonic mucus layers was significantly reduced when compared with unstirred layers (P &lt; 0.05). Whether this has an effect on the butyrate supply to colonocytes in vitro and whether mucus in colonic disease behaves differently are subjects for further investigation.
Changes in bone and muscle constituents during dieting for obesity
Authors: Davie Michael W. J. , Abraham Ralph R. , Hewins Belinda , Wynn Victor 
Published: August 2015

1. The effects of dietary carbohydrate (CHO) content and of tri-iodothyronine (T3) administration on calcium, zinc and phosphate balances and on urinary hydroxyproline output were examined in eight obese subjects undergoing therapy with low energy (2741–3301 kJ/day), high calcium (28.9–35.1 mmol/day) diets.
2. Calcium balances were generally positive at the high levels of intake used, but significantly more calcium was retained when dietary CHO intake (as proportion of total energy intake) was increased.
3. Zinc balances were more positive when the proportion of dietary CHO was high and correlated both with nitrogen balance and with daytime insulin concentration.
4. Urinary hydroxyproline output generally increased with dieting irrespective of dietary CHO content.
5. Administration of T3 (30–80 μg/day) markedly increased zinc loss without affecting calcium balance.