bluuebunny/crossref_metadata_2025_split huggingface dataset:
Factors contributing to the accelerated clearance of theophylline and antipyrine in adults with exocrine pancreatic disease
Authors: Acheson David W. K. , Hunt Linda P. , Rose Patricia , Houston J. Brian , Braganza Joan M. 
Published: August 2015

1. Oxidative drug metabolizing capacity has been assessed by oral antipyrine and/or theophylline tests in consecutive patients with chronic pancreatitis (CP; alcoholic 24, idiopathic 47), acute pancreatitis (AP; 28) and pancreatic cancer (CA; 11). Most of the patients had drastically reduced their alcohol consumption and dietary fat intake for variable periods before the tests. Excellent bioavailability of theophylline was confirmed from paired oral and intravenous tests in seven subjects, including two with exocrine pancreatic failure.
2. The clearance of theophylline in the patients was faster than in 15 controls with a ‘healthy lifestyle’ [median 104 (range 18–320) ml h−1 kg−1 vs median 68 (range 50–97) ml h−1 kg−1, P &lt; 0.01]. The difference was especially apparent in the groups with alcoholic CP (P &lt; 0.001 and idiopathic CP (P &lt; 0.01), but not in the AP and CA group as a whole, although drug clearance in some 50% of those cases exceeded the reference range.
3. There was good correlation between theophylline and antipyrine clearance in a subset of 91 subjects who had both tests (15 controls, 76 patients), but antipyrine was much less sensitive as a marker of enzyme induction. This suggests that enzyme induction in pancreatic disease preferentially involves the polycyclic aromatic hydrocarbon-inducible subfamily of cytochrome P-450.
4. The lack of correlation between pancreatic secretory capacity in 56 cases, judged by a secretin-pancreozymin test, and theophylline clearance suggests that enzyme induction is not secondary to pancreatic dysfunction.
5. Multivariate regression analysis identified approximately 50% of variability in clearance of each probe. For theophylline, smoking and dietary protein were identified as inducers, whilst certain drugs, alcohol and methylxanthines emerged as inhibitors: the highest theophylline clearance values were shared equally between smokers and non-smokers. For antipyrine, smoking and protein had a positive influence.
6. We cannot tell from the study whether enzyme induction is an epiphenomenon or contributes to the pathogenesis of CP, AP and CA. If future studies prove the latter, the corollary may be that xenobiotics which are inducers of and/or processed by the polycyclic aromatic hydrocarbon-inducible subfamily of cytochrome P-450 are aetiological factors in exocrine pancreatic disease.
Increased lysine transport capacity in erythrocytes from patients with chronic renal failure
Authors: Fervenza F. C. , Harvey C. M. , Hendry B. M. , Ellory J. C. 
Published: August 2015

1. The initial rate of l-lysine influx into erythrocytes from 13 patients with chronic renal failure has been measured using 14C-labelled lysine. Ten patients were on maintenance haemodialysis and three had never been dialysed. The results are compared with data obtained from 12 normal individuals.
2. The rate of lysine influx into washed cells from buffered saline containing 0.02–0.5 mmol of l-lysine/l has been calculated. The results can be fitted with a model in which influx has a single saturable component obeying Michaelis–Menten kinetics, and a linear non-saturable component.
3. In uraemic erythrocytes the saturable component had a mean Vmax. of 0.762 mmol h−1 litre−1 of cells (n = 13, sem 0.072) and a mean Km of 68.2 μmol/l (sem 5.7). These values in normal erythrocytes were 0.566 mmol h−1 litre−1 of cells (n = 12, sem 0.033) and 70.5 μmol/l (sem 4.1), respectively. The mean apparent diffusion constant (KD) for the linear component of influx was 0.224 h−1 (sem 0.039) in uraemic cells and 0.178 h−1 (sem 0.028) in normals.
4. The 35% increase in mean Vmax. seen in uraemic erythrocytes was statistically significant (P = 0.02). A similar increase in Vmax. in uraemic cells compared with controls was seen in erythrocytes which were studied in zero-trans conditions after depletion of intracellular amino acids. The mean values of Km and KD were not significantly different in uraemia. The origins of this increased membrane transport capacity for lysine in uraemia are discussed.
Inactive plasma renin exhibits sex difference in mice
Authors: Nielsen Arne Høj , Johannessen Arne , Poulsen Knud 
Published: August 2015

1. The plasma concentration of inactive renin was two-to three-fold higher in male than in female mice independently of whether mice of strains with low (BALB/c) or high (Theiller) content of active renin in the submandibular salivary glands were studied.
2. Removal of the submandibular glands did not affect the high plasma concentration of inactive renin in male mice.
3. Inactive plasma renin decreased over several days after castration of normal and sialoadenectomized male mice to the same levels as those found in normal female mice.
4. Treatment of these castrated male mice with testosterone increased and normalized inactive plasma renin independently of whether the submandibular glands had been previously removed or not.
5. Testosterone treatment of sialoadenectomized female mice increased inactive renin to the same levels as those found in normal male mice.
6. Our findings suggest that the sex difference in inactive plasma renin in mice may be explained by an increased secretion of inactive renin in male mice stimulated by androgens.
7. Since we have recently found that inactive plasma renin in male mice is mainly of renal origin, this increased secretion is most likely located to the kidneys.
Stimulation by uraemic plasma of frusemide-sensitive sodium efflux in erythrocytes from normal women
Authors: Corry Dalila B. , Tuck Michael L. , Lee David B. N. 
Published: August 2015

1. Reduced Na+, K+ pump activity has been reported in uraemic erythrocytes, and this has been attributed to the presence of a circulating ouabain-like inhibitor. Since we have previously reported marked suppression of Na+, K+ co-transport activity in erythrocytes from dialysis patients, we have now examined the effect of incubation with uraemic plasma on Na+ efflux through the Na+, K+ pump and the co-transport pathway in normal erythrocytes from both men and women.
2. The results show that Na+ efflux via the Na+, K+ pump is not different between men and women (3.14 ± 0.14 vs 3.68 ± 0.18 mmol h−1 litre−1 of cells) and is not inhibited by incubation with uraemic plasma.
3. In contrast, co-transport-mediated Na+ efflux is lower in erythrocytes from normal women when compared with normal men (0.17 ± 0.02 vs 0.25 ± 0.05 mmol h−1 litre−1 of cells, P &lt; 0.001).
4. Moreover, incubation with uraemic plasma causes stimulation of Na+ efflux through the co-transport pathway in erythrocytes of healthy women (0.17 ± 0.02 vs 0.27 ± 0.03 mmol h−1 litre−1 of cells, P &lt; 0.005), but not in erythrocytes of healthy men (0.27 ± 0.03 vs 0.25 ± 0.05 mmol h−1 litre−1 of cells).
5. Our data do not support the presence of either a Na+, K+ pump or a co-transport inhibitor in plasma from dialysed uraemic patients. Thus, the suppressed co-transport activity demonstrated in uraemic erythrocytes cannot be attributed to a circulating inhibitor, and may reflect an acquired membrane or transport defect.
6. The stimulation of co-transport by uraemic plasma from women provides a further example of sex-determined characteristics in human erythrocytes, the mechanism of which remains to be elucidated.
Correlation of blood pressure in normotensive and hypertensive individuals with platelet but not lymphocyte intracellular free calcium concentrations
Authors: Pritchard K. , Raine A. E. G. , Ashley C. C. , Castell L. M. , Somers V. , Osborn C. , Ledingham J. G. G. , Conway J. 
Published: August 2015

1. Fifty-two normotensive and essential hypertensive subjects were studied. Intracellular free calcium concentration ([Ca2+]i) was measured in lymphocytes (37 subjects) and platelets (18 subjects) by means of the fluorescent indicators, quin 2 and fura-2. In 31 subjects, plasma ionized calcium concentration was also measured.
2. There was a positive correlation between platelet [Ca2+]i and systolic blood pressure (r = 0.485, P &lt; 0.05), diastolic blood pressure (r = 0.542, P &lt; 0.02) and mean blood pressure (r = 0.534, P &lt; 0.02).
3. No statistically significant relationship was observed between plasma ionized calcium and blood pressure.
4. No relationship was found between lymphocyte [Ca2+]i and blood pressure, or between lymphocyte [Ca2+]i and plasma ionized calcium.
5. There was no relationship between [Ca2+]i of lymphocytes and platelets measured simultaneously from the same subject.
6. These findings reconcile previous conflicting reports and show a relationship between platelet but not lymphocyte [Ca2+]i and blood pressure in man.
Naloxone-Reversible Inhibition of Gall-Bladder Mucosal Fluid Secretion in Experimental Cholecystitis in the Cat by Acetorphan, an Enkephalinase Inhibitor
Authors: Jivegård L. , Pollard H. , Moreau J. , Schwartz J. C. , Thune A. , Svanvik J. 
Published: August 2015

1. Enkephalin immunoreactive nerve fibres have been demonstrated in the gall bladder of various mammals including man. In various tissues, enkephalins are partly degraded by a membrane metallo-endopeptidase, enkephalinase (EC 3.4.24.11).
2. Using 3H-labelled [d-Ala2,Leu5]enkephalin as a substrate, enkephalinase activity, immunoprecipitated by a monoclonal antibody directed against the rabbit kidney enzyme, was demonstrated in the feline gall bladder. Using the same antibody in 125I-labelled form, the peptidase was immunolocalized by autoradiography, mainly in the epithelium.
3. In experimental cholecystitis, elicited by implantation of human gall-stones into the cat gall bladder, the continuous fluid secretion into the lumen was inhibited by exogenous enkephalins.
4. Acetorphan, an enkephalinase inhibitor, was found to block fluid secretion by the inflamed gall bladder via a naloxone-sensitive mechanism, but not to affect fluid transport in the normal gall bladder. The drug also transiently contracted the gall bladder and increased bile outflow from the liver.
5. It is suggested that acetorphan, by reducing the degradation of endogenous enkephalins in the inflamed gall bladder, decreases fluid secretion by the epithelium and that enkephalinase inhibitors may find clinical applications in acute cholecystitis.
Differential Blood Pressure and Hormonal Effects after Glucose and Xylose Ingestion in Chronic Autonomic Failure
Authors: Mathias C. J. , da Costa D. F. , McIntosh C. M. , Fosbraey P. , Bannister R. , Wood S. M. , Bloom S. R. , Christensen N. J. 
Published: August 2015

1. To investigate whether carbohydrate contributes to postprandial hypotension in autonomic failure, the cardiovascular, biochemical and hormonal effects of oral glucose and an iso-osmotic solution of oral xylose were studied on separate occasions in six patients with chronic autonomic failure. The effects of oral glucose were also studied in eight normal subjects.
2. In the patients oral glucose lowered blood pressure substantially (−34 ± 7% at 60 min, area under curve −24.9 ± 3.5%, P &lt; 0.001) and for a prolonged period (− 25 ± 4% at 120 min). Plasma noradrenaline levels did not change. In the normal subjects blood pressure was unchanged and plasma noradrenaline rose, suggesting a compensatory increase in sympathetic nervous activity.
3. In the patients xylose caused a smaller and more transient fall in blood pressure (−15 ± 6% at 90 min, area under curve −8.9 ± 4%, P &lt; 0.05) with a non-significant elevation in packed cell volume (36.7 ± 1.8 to 38.2 ± 1.8). It was therefore unclear if xylose was exerting osmotic effects within the bowel which contributed to the small blood pressure fall. Packed cell volume did not change in either the patients or normal subjects after glucose.
4. In the patients and normal subjects plasma insulin rose after glucose. Insulin levels were unchanged after xylose. Levels of pancreatic polypeptide and neurotensin, a potential vasodilator, rose in the patients only. The latter rose to a similar extent after both glucose and xylose, making it unlikely that neurotensin alone accounted for the hypotension.
5. These studies indicate that the carbohydrate components of a meal, and in particular those causing insulin release, contribute to postprandial hypotension in patients with autonomic failure.
Intestinal Infection with Nematospiroides Dubius Selectively Increases Lactase Expression by Mouse Jejunal Enterocytes
Authors: Smith M. W. , Lloyd S. 
Published: August 2015

1. Intestinal structure, lactase (β-galactosidase; EC 3.2.1.23) activity and alkaline phosphatase activity have been determined in mouse jejunal and ileal tissues before and during infection with the intestinal parasite Nematospiroides dubius.
2. Oral infection with small numbers of N. dubius larvae caused villus height, crypt depth and enterocyte migration rate to increase in the mouse jejunum. None of these effects occurred in ileal tissue.
3. Lactase activity also increased in jejunal, but not ileal, tissue of infected mice. This increase was associated with a doubling of the rate at which activity appeared in the brush-border membrane of enterocytes during migration over the basal regions of jejunal villi. Alkaline phosphatase activity in jejunal tissue remained unchanged in infected mice.
4. Attention is drawn to the fact that this is the first occasion when crypt cell hyperplasia has been found to be positively correlated with an increase in lactase activity and a decrease in cytotoxic/suppressor T-cells. Further work is needed to establish the primary cause of these effects.
Erythrocyte Membrane Calcium Adenosine 5′-Triphosphatase Activity in the Spontaneously Hypertensive Rat
Authors: Adeoya Abimbola S. , Norman Robert I. , Bing Robert F. 
Published: August 2015

1. Ca2+-adenosine 5′-triphosphatase (Ca2+ −Mg2+ – ATPase) activity was studied simultaneously in calmodulin-deficient erythrocyte ghost membranes and inside-out vesicles (IOVs) from 12-week-old female spontaneously hypertensive rats (SHR) and their matched controls: [Wistar-Kyoto normotensive rats (WKY)], and in detergent extracts of ghost membranes.
2. Both adenosine 5′-triphosphate (ATP)-dependent Ca2+ uptake by IOVs and Ca2+-dependent ATP hydrolysis activity of ghost membranes were reduced significantly in the SHR compared with WKY, when either the calmodulin-independent or calmodulin-stimulated activities were compared.
3. The ratios between Ca2+ uptake and ATP hydrolysis activities in the SHR remained approximately 1.0, showing a proportional reduction in both activities.
4. No difference in affinity for calmodulin was observed between SHR and WKY.
5. No significant difference in Ca2+-dependent ATP hydrolysis activity was observed between SHR and WKY after detergent solubilization of erythrocyte ghost membranes.
6. These results suggest that the number of Ca2+-Mg2+-ATPase units are similar in SHR and WKY and that the reduced activity in the intact SHR membrane is due to altered membrane environment.
Effect of a High Protein Diet in Patients with the Nephrotic Syndrome
Authors: Mansy H. , Goodship T. H. J. , Tapson J. S. , Hartley G. H. , Keavey Pauline , Wilkinson R. 
Published: August 2015

1. Twelve patients with the nephrotic syndrome were prescribed for 4 week periods a normal protein diet (NPD) containing 1 g of protein/kg ideal body weight. They were then prescribed for further 4 week periods in random order diets with high (HPD) and low (LPD) protein contents, respectively 2.0 and 0.5 g/kg ideal body weight.
2. Compliance was confirmed by dietary history and measurement of urinary urea excretion.
3. Serum albumin was the same on all diets. Twenty-four hour urinary protein excretion increased progressively with increasing dietary protein (LPD 6.1 g, NPD 8.2 g, HPD 9.2 g). Recumbent plasma renin activity and serum phosphate were significantly increased on HPD (plasma renin activity: LPD 5.7, NPD 4.6, HPD 8.2 pmol of angiotensin I min−1 I−1; serum phosphate: LPD 1.27, NPD 1.26, HPD 1.41 mmol/l).
4. There was no evidence of protein-induced hyperfiltration or hyperperfusion: 51Cr-ethylenediaminetetraacetate and [125I]iodohippurate clearances were similar on all three diets.
5. Since proteinuria, increased plasma renin levels and hyperphosphataemia may contribute to progression of renal failure and because HPD did not improve hypoalbuminaemia, the use of HPD in the nephrotic syndrome should be abandoned.
6. Until it can be established that LPD, which is accompanied by the least proteinuria, does not, with long-term feeding, lead to malnutrition, NPD should be used in the treatment of the nephrotic syndrome.
Cardiovascular Reflex Responses in Patients with Unexplained Syncope
Authors: Wahbha M. M. A. E. , Morley C. A. , Al-Shamma Y. M. H. , Hainsworth R. 
Published: August 2015

1. This study was undertaken to determine whether, in a group of patients complaining of recurrent syncopal attacks but with no apparent cause, there was evidence of abnormal cardiovascular reflex control.
2. The steady-state responses of blood pressure, heart rate and cardiac output to head-up tilting were determined in 67 patients using entirely ‘non-invasive’ methods. In some patients we also studied the immediate response of pulse interval to carotid baroreceptor stimulation by neck suction.
3. Two of the patients developed vasovagal attacks during the 20 min test period of head-up tilting. Eighteen others showed postural hypotension, defined as a fall in blood pressure to outside the limits of two sds from the mean values of age-related control subjects.
4. Patients who showed postural hypotension had a mean fall in cardiac output significantly larger than that in age-related control subjects. Responses in the non-hypotensive patients did not differ significantly from controls.
5. Stimulation of carotid baroreceptors resulted in significantly smaller responses of pulse interval in the patients defined as having postural hypotension compared with the non-hypotensive patients and with the age-related control subjects.
6. In some of the patients who did not show postural hypotension during the standard test, the duration of tilt was prolonged for up to 1 h. Five out of 26 patients developed vasovagal attacks. All the vasovagal patients showed an initial tachycardia and the response of pulse interval to neck suction was significantly larger than in the controls.
7. This study has shown that simple non-invasive tests of cardiovascular reflex function can divide patients with poor orthostatic tolerance into two groups: those with evidence of small reflex responses, associated with abnormally large falls in cardiac output during tilting, and those with evidence of overactive reflexes associated with the tendency to develop vasovagal syncope.
Effects of Endothelin on Systemic and Renal Haemodynamics and Neuroendocrine Hormones in Conscious Dogs
Authors: Nakamoto Hidetomo , Suzuki Hiromichi , Murakami Marohito , Kageyama Yo , Ohishi Akira , Fukuda Keiichi , Hori Shingo , Saruta Takao 
Published: August 2015

1. The effects of endothelin on systemic and renal haemodynamics and plasma concentrations of neuroendocrine hormones including plasma renin activity, aldosterone, adrenocorticotropic hormone, Cortisol, catecholamines and arginine vasopressin were investigated in 18 conscious dogs.
2. Bolus injection of 4 pmol of endothelin/kg did not cause any significant changes in haemodynamics. Mean arterial pressure was elevated by both doses of 40 pmol/kg [91 ± 2 to 99 ± 2 mmHg (12.1 ± 0.3 to 13.2 ± 0.3 kPa), P &lt; 0.05] or 200 pmol/kg [93 ± 2 to 107 ± 3 mmHg (12.4 ± 0.3 to 14.3± 0.4 kPa), P &lt; 0.01], the latter dose increasing cardiac output (14%, P &lt; 0.05) and heart rate (9%, P &lt; 0.05), and the former reducing these parameters (14% and 8%, P &lt; 0.05, respectively).
3. In contrast with the various changes in systemic haemodynamics, renal blood flow transiently increased immediately after bolus injection in a dose-dependent manner (28%, P &lt; 0.05, 50%, P &lt; 0.01 and 110%, P &lt; 0.01 with 4, 40 and 200 pmol of endothelin/kg, respectively). This transient elevation of renal blood flow was followed by a gradual decrease (16%, P &lt; 0.05; 31%, P &lt; 0.01 and 36%, P &lt; 0.01) at 10 min.
4. All neurohormones were elevated in a dose-dependent manner.
5. Among these hormones, arginine vasopressin and plasma renin activity reached a peak level at 5 min (from 2.21 ± 0.45 to 6.37 ± 0.60 pmol/l, P &lt; 0.01, and from 0.65 ± 0.08 to 1.09 ± 0.10 pmol of angiotensin 1 h−1 ml−1P &lt; 0.01, respectively) after bolus injection of 200 pmol of endothelin/kg, whereas adrenocorticotropic hormone and Cortisol reached a peak level at 15 min (from 6.0 ± 0.7 to 18.2 ± 1.5 pmol/l, P &lt; 0.01, and from 4.4 ± 0.9 to 16.5 ± 2.7 × 10−2 μmol/l, P &lt; 0.01, respectively).
6. These results suggest that endothelin is a potent vasoconstrictive peptide in vivo with a marked effect on the renal vascular system, and that it induces elevation of vasoactive hormones directly and/or through central effects.
Mineralocorticoid activity of carbenoxolone: contrasting effects of carbenoxolone and liquorice on 11β-hydroxysteroid dehydrogenase activity in man
Authors: Stewart P. M. , Wallace A. M. , Atherden S. M. , Shearing C. H. , Edwards C. R. W. 
Published: August 2015

1. 11β-Hydroxysteroid dehydrogenase is an enzyme complex consisting of 11β-dehydrogenase and 11-oxoreductase responsible for the interconversion of cortisol to cortisone in man. Inhibition of 11β-dehydrogenase (e.g. after liquorice ingestion) results in cortisol acting as a potent mineralocorticoid. We have evaluated the effect of the synthetic liquorice derivative, carbenoxolone, on this enzyme complex.
2. Carbenoxolone given to six volunteers in metabolic balance produced sodium retention with suppression of the renin-angiotensin-aldosterone system. Plasma potassium fell, although there was no kaliuresis. This was associated with inhibition of 11β-dehydrogenase (as measured by a rise in the plasma half-life of [11α-3H]-cortisol). Unlike liquorice, however, carbenoxolone also inhibited 11-oxoreductase (as measured by the generation of cortisol after oral cortisone acetate).
3. The mineralocorticoid activity of carbenoxolone, like liquorice, is mediated via cortisol by inhibition of 11β-dehydrogenase. Carbenoxolone, however, also inhibits 11-oxoreductase activity and this may relate to its effect on renal potassium excretion.
Blood pressure, left ventricular mass and intracellular calcium in primary hyperparathyroidism
Authors: Dominiczak Anna F. , Lyall Fiona , Morton James J. , Dargie Henry J. , Boyle Iain T. , Tune Tan T. , Murray Gordon , Semple Peter F. 
Published: August 2015

1. Blood pressure, left ventricular mass and platelet cytosolic free calcium concentrations were measured in 23 patients with untreated primary hyperparathyroidism, 30 normotensive control subjects and 23 control subjects matched for age, sex and blood pressure. In 12 patients measurements were repeated after parathyroidectomy.
2. Patients with primary hyperparathyroidism had significantly elevated blood pressures (139 ± 6/86 ± 3 mmHg, mean ± sem) compared with control subjects (125 ± 2/78 ± 1 mmHg), but high values persisted after hypercalcaemia was corrected.
3. Despite chronic extracellular hypercalcaemia, intracellular free calcium levels were lower in patients with hyperparathyroidism than in controls matched for age, sex and blood pressure (median concentrations 81.5 nmol/l vs 93 nmol/l, 95% confidence interval 0.1 to 20.1; P &lt; 0.05) and values tended to increase after parathyroidectomy.
4. Left ventricular mass index was increased in the primary hyperparathyroid group as compared with control subjects matched for age, sex and blood pressure (123 g/m2 vs 100 g/m2, 95% confidence interval −36.1 to −3.1; P = 0.03). Parathyroidectomy resulted in a small reduction of the left ventricular mass index (123.5 g/m2 vs 104 g/m2, 95% confidence interval 46.5 to 2.5; P = 0.1) but no change in blood pressure.
5. Hypertension and left ventricular hypertrophy in primary hyperparathyroidism are associated with relatively low levels of free calcium in platelets.