bluuebunny/crossref_metadata_2025 huggingface dataset:
Inhibition of Jejunal Water and Electrolyte Absorption by Therapeutic Doses of Clindamycin in Man
Authors: Spiller R. C. , Higgins B. E. , Frost P. G. , Silk D. B. A.
Published: August 2015

1. A steady-state perfusion technique has been used in vivo in normal subjects to show that at concentrations occurring during therapeutic use (500 mg/l, 1.1 mmol/l) the antibiotic clindamycin reversibly inhibits bicarbonate-stimulated water and electrolyte absorption from the human jejunum.

2. Lactose-stimulated water and electrolyte absorption was not affected by the addition of clindamycin at the same concentration.

3. Clindamycin-induced malabsorption of water and electrolytes may contribute significantly to the diarrhoea that occurs during clindamycin therapy in the absence of pseudomembranous colitis.
Comparison between short-term Renal Haemodynamic Effects of Propranolol and Nadolol in Essential Hypertension: A Crossover Study
Authors: Danesh Boothur J. Z. , Brunton Joyce , Sumner David J.
Published: August 2015

1. The effect of 4-6 weeks’ treatment with propranolol and nadolol on effective renal plasma flow (ERPF) and glomerular filtration rate (GFR) was studied, in 14 patients with essential hypertension, in single blind, random and cross-over design.

2. Both drugs caused comparable effective lowering of pulse and blood pressure.

3. When taken as the first drug, propranolol caused significant reduction in ERPF and GFR and a rise in filtration fraction (FF) and renal vascular resistance (RVR), whereas nadolol caused distinct rise in ERPF and a fall in FF and RVR but GFR remained unchanged.

4. These haemodynamic effects were reduced when propranolol was given immediately after the withdrawal of nadolol and were obviated when nadolol followed propranolol therapy. This suggested a carry-over effect of the first drug into the second phase of treatment.

5. We conclude that with short term therapy in essential hypertension, propranolol has a renal vasoconstrictor and nadolol a vasodilator effect.
The Temporal Distribution of the 1α,25-Dihydroxycholecalciferol Receptor in the Rat Jejunal Villus
Authors: Chan S. D. H. , Atkins D.
Published: August 2015

1. The distribution of the 1α,25-dihydroxycholecalciferol receptor was studied in enterocytes isolated from the upper, mid and lower villus and crypt cells of the jejunum of normal and rachitic rats.

2. In all cell fractions a high-affinity receptor (KD ⋍ 0.07 nmol/l) with a sedimentation coefficient of 3.5S was demonstrated.

3. In normal rats there was a 60% reduction in receptor numbers in crypt cells compared with the mid and upper villous cells.

4. Vitamin D deficiency led to a reduction in receptor numbers in all cell fractions (45% upper villus, 78% crypt cells).

5. The data are compatible with the concept of calcium absorption occurring in the differentiated villous cells and also account for the reduction in absorption in rachitic animals.
Glycogen Metabolism in Psoriatic Epidermis and in Regenerating Epidermis
Authors: Harmon C. S. , Phizackerley P. J. R.
Published: August 2015

1. The observation that the glycogen content of epidermis from psoriatic lesions and from regenerating wound epithelium is increased has been confirmed by quantitative estimation.

2. In epidermis from psoriatic lesions, although the proportion of glycogen synthase in the I form is only about 5% of the total and similar to control values, total glycogen synthase activity is increased approximately 4-fold and hence glycogen synthase I activity is increased to the same extent. In contrast, total phosphorylase activity is only slightly increased and, since the proportion of the enzyme in the a form is reduced, phosphorylase a activity is similar to control values.

3. In epidermis from psoriatic lesions, the concentration of UDP-glucose is approximately doubled, and the concentrations of fructose 1,6-bisphosphate and of 6-phosphogluconate are increased approximately 5-fold. It is concluded that rates of glycogen synthesis, of glycolysis and of the pentose phosphate pathway are all enhanced in vivo and in consequence the rate of glucose uptake by psoriatic epidermis must be increased.

4. In the non-involved epidermis of psoriatic patients the glycogen content is within normal limits, and although total glycogen synthase activity is increased the ratio of glycogen synthase I to phosphorylase a is maintained at normal levels by the appropriate phosphorylation of both enzymes.

5. In regenerating wound epithelium in the pig, the changes in enzyme activity and in metabolite concentration closely resemble those found in epithelium from psoriatic lesions except that in wound epithelium the proportion of phosphorylase in the a form is increased relative to normal epithelium.
The Regulatory Roles of Liver and Kidney in Cobalamin (Vitamin B12) Metabolism in the Rat: the Uptake and Intracellular Binding of Cobalamin and the Activity of the Cobalamin-Dependent Enzymes in Response to Varying Cobalamin Supply
Authors: Scott J. S. D. , Treston A. M. , Bowman E. P. W. , Owens J. A. , Cooksley W. G. E.
Published: August 2015

1. To examine possible regulatory roles of liver and kidney in cobalamin metabolism, specific activities of the two cobalamin-dependent enzymes, uptake in vivo of cyano[57Co]cobalamin ([57Co]CNCbl) and the binding of [57Co]Cbl to intracellular proteins were measured in normal, cobalamin-loaded and cobalamin-deficient rats. Cobalamin deficiency and cobalamin loading produced greater changes in cobalamin concentration in the kidney than in the liver.

2. Although cobalamin deficiency resulted in a decrease in total methylmalonyl-coenzyme A mutase (methylmalonyl-CoA mutase) in both organs, cobalamin loading had no effect. Neither deficiency nor loading altered total methyltransferase activity. The holoenzyme activities of both enzymes correlated with changes in tissue cobalamin levels.

3. Uptake of [57Co]Cbl indicated that the kidney, in contrast to the liver, increased its uptake during loading and reduced it during deficiency, suggesting a possible regulatory role for this organ.

4. In the normal rat, 24 h after injection of [57Co]CNCbl, 0.3% of the administered [57Co]Cbl was present in the liver as free cobalamin. By contrast, in the kidney, over 13% of the [57Co]Cbl was present in the free form. During deficiency free renal [57Co]Cbl was reduced to 0.6% of the administered [57Co]Cbl whereas in cobalamin-loaded rats it was increased to more than 27%.

5. It is concluded that alterations in tissue cobalamin levels resulting from differences in cobalamin supply are due to changes in the large pool of free cobalamin present in the kidney and not to changes in the intracellular binding.
Glucocorticoid Inhibition of Mineralocorticoid Action in the Rat
Authors: Kenyon C. J. , Saccoccio N. A. , Morris D. J.
Published: August 2015

1. The mineralocorticoid activity of corticosterone based on acute changes in urinary Na+/K+ ratios in adrenalectomized rats was 1000 times less than that of aldosterone. However, corticosterone had only kaliuretic actions whereas aldosterone had both antinatriuretic and kaliuretic properties. Corticosterone inhibited the antinatriuretic actions of aldosterone.

2. Adrenalectomized rats infused continuously with a physiological dose of corticosterone (1 mg/day) were 5 times less sensitive to the antinatriuretic and 25 times less sensitive to the kaliuretic actions of aldosterone when administered acutely than were control adrenalectomized rats.

3. The long term effects of infusions of physiological doses of aldosterone and corticosterone were assessed in adrenalectomized rats maintained in metabolic cages. Aldosterone lowered plasma renin activity and reduced fluid (0.3% NaCl) intake; these effects were diminished when aldosterone and corticosterone were infused simultaneously. Plasma renin activity and fluid intake were correlated in long term infusion experiments. Both hormones had hypokalaemic effects but these were not additive. Corticosterone, but not aldosterone, increased systolic blood pressure and plasma sodium levels.

4. We conclude that glucocorticoid effects on water and electrolyte metabolism are different from those of mineralocorticoids, that glucocorticoids may antagonize mineralocorticoid effects and that interactions between mineralocorticoids and glucocorticoids may be important in long term blood pressure regulation.
Enzymatic Activity of Renin in Plasma of Normal and Uraemic Subjects
Authors: Kotchen Theodore A. , Guyenne Tam T. , Corvol Pierre , Menard Joel
Published: August 2015

1. Plasma renin reactivity (PRR) is the rate of angiotensin I production after addition of renin to plasma, minus endogenous renin activity. PRR is increased in plasma of patients with renal failure compared with that of normal subjects. The present study was carried out to determine if increased PRR in uraemic plasma is related to differences of endogenous active or inactive renin, endogenous renin substrate, or pH of the incubation in vitro.

2. PRR in plasma of ten uraemic patients was greater (P<0.02) than that in plasma of ten normal subjects in incubations carried out at pH 7.4 and 5.7.

3. Increased PRR was not accounted for by differences of endogenous active and inactive renin activity.

4. After addition of renin, renin concentration (measured by direct radioimmunoassay) did not differ in normal and uraemic plasma.

5. Renin substrate concentration, measured both indirectly and by direct radioimmunoassay, also did not differ in normal and uraemic plasma.

6. Increased PRR in uraemic plasma is not related to alterations of renin or renin substrate concentrations. These observations are consistent with our earlier hypothesis that there is a deficiency of a renin inhibitor in uraemic plasma.
Angiotensin Converting Enzyme Response to Hypoxia in Man: Its Role in Altitude Acclimatization
Authors: Milledge J. S. , Catley D. M.
Published: August 2015

1. The response of serum angiotensin converting enzyme (ACE) activity to three grades of hypoxia was studied in two groups of human subjects. Hypoxic gas mixtures having oxygen concentrations of 14, 12.6 and 10.4% were breathed successively for a period of 10 min at each concentration. Venous blood was sampled at the end of each of the three periods and arterial oxygen saturation was recorded throughout the experiment.

2. The subjects were selected as being ‘good’ or ‘poor’ acclimatizers according to their history of acute mountain sickness. There were five subjects in each group.

3. Hypoxia resulted in a reduction in ACE activity in both groups, the reduction being linear with respect to arterial oxygen saturation.

4. The reduction in ACE activity was greater in the good acclimatizer group as shown by a significantly greater slope of the response line of ACE activity to arterial oxygen saturation.

5. The significance of this finding in relation to the mechanism underlying acute mountain sickness is discussed.
Distribution of Dead Space Volume in the Human Lung
Authors: Tatsis George , Horsfield Keith , Cumming Gordon
Published: August 2015

1. The first four breaths from a multi-breath nitrogen wash-out have been analysed in 20 normal subjects by differentiation and data smoothing of phase II of the expired concentrations of nitrogen and carbon dioxide.

2. This procedure yields a distribution curve which is skewed to the right, the mode of which represents the usual value of dead space. The minimum and maximum values were found by excluding 2.5% of data points at each end of the distribution.

3. The values of minimum, mode and maximum in men were 67.6, 147 and 300 ml. For women the values were 55.4, 109 and 235 ml.

4. It is suggested that this distribution reflects the asymmetrical nature of the bronchial tree and comparison with anatomical data suggests that anatomy is the principal determinant of the distribution of dead space.

5. The contribution made by the spread of the stationary interface within individual bronchioles is evident but small.
Progression to Renal Failure after Nephrotoxic Nephritis in Rats Studied by Renal Transplantation
Authors: El Nahas A. M. , Lechler R. , Zoob S. N. , Rees A. J.
Published: August 2015

1. We studied the relation between immunopathology and progressive renal failure after nephrotoxic nephritis (NTN) in rats.

2. Thirty days after induction of nephritis by injection of rabbit anti-rat nephrotoxic serum, pairs of kidneys from 13 nephritic rats were transplanted into separate syngeneic recipients, one of whom had been pre-immunized with rabbit immunoglobulin G (IgG) whilst the other was naive.

3. Progression to renal failure of the transplanted nephritic kidney was studied after removal of the recipient's own kidneys; results from right and left kidney from a single donor in pre-immunized and naive recipients were compared.

4. There were substantial differences in autologous anti-rabbit IgG titres in naive and pre-immunized recipients; despite this pairs of kidneys from the same donor had almost identical courses as assessed by proteinuria, serum creatinine and graft survival.

5. There was substantial variation in survival of kidneys from different donors. But there were very strong correlations of graft survival with proteinuria (r = 0.97, t = 4.443, P<0.001) and reciprocal serum creatinine (r = 0.95, t = 4.32, P<0.001) in donors shortly before transplantation.

6. We conclude that autologous antibody titres did not influence the progression to renal failure after nephrotoxic nephritis. The rate of progression was already determined at the time of transplantation.
Evidence of Parasympathetic Activity of the Angiotensin Converting Enzyme Inhibitor, Captopril, in Normotensive Man
Authors: Campbell B. C. , Sturani Alessandra , Reid J. L.
Published: August 2015

1. Captopril (50 mg orally) produced a significant fall in systolic and diastolic blood pressure in six normotensive sodium replete subjects, without a rise in heart rate.

2. On captopril, there was no change in the expected normal increase in heart rate on standing. Supine plasma noradrenaline was not reduced by captopril and normal postural increases were maintained.

3. Atropine (0.04 mg/kg i.v.) reduced the difference in blood pressure change between captopril and placebo.

4. Facial immersion in water produced a bradycardia. This change was abolished by atropine and attenuated both by captopril and edrophonium (10 mg i.V.), a cholinesterase inhibitor.

5. Lying down after 6 min standing produced an immediate transient tachycardia, which was abolished by atropine and attenuated by captopril.

6. Blood pressure and heart rate rose after a cold pressor test on both captopril and placebo.

7. The tachycardia during the Valsalva manoeuvre was inhibited by edrophonium and to a lesser extent by captopril. The effects of captopril and edrophonium were additive.

8. Parasympathetic activity of captopril may contribute to its haemodynamic profile.
Optimal Conditions for Measurement of Na+, K+-ATPase Activity of Human Leucocytes
Authors: Baron D. N. , Khan F. A.
Published: August 2015

1. The Na+, K+-ATPase activity of human leucocytes was assayed by measuring the release of inorganic phosphate (Pi) from ATP.

2. The maximum enzyme activity was achieved under the following conditions: concentration (mmol/l), Tris/HCl 50, Na 100, K 15, ATP 5, Mg 7, EDTA 1; pH 7.2 and temperature 37°C, were optimal. Ouabain showed maximal inhibition at a concentration of 10-100 μmol/l. Ethanol, the solvent for ouabain, had a dose-related inhibitory effect.

3. Heparin or citrate used as an anticoagulant gave similar results. Leucocyte samples could be stored at −20°C for up to 6 days without loss of activity. Hypotonic lysis had advantages over sonication as the technique for cell disruption.

4. The leucocyte Na+, K+-ATPase enzyme activity in healthy subjects was 186 μmol of Pi h−1 g−1 of protein (median) with a range 136-243 μmol of Pi h−1 g−1 of protein. The within-batch coefficient of variation was 6.4% and the between-batch precision was 9.6%.
Haemodynamic and Endocrine Responses of the Kidney to Frusemide in Mild Essential Hypertension
Authors: Mackay I. G. , Nath K. , Cumming A. D. , Muir A. L. , Watson M. L.
Published: August 2015

1. Prostaglandin-dependent, frusemide-induced changes in renal plasma flow, glomerular filtration rate and plasma renin activity were measured in 14 patients with mild essential hypertension.

2. The renal haemodynamic responses to frusemide were the same as in 10 normal subjects.

3. Frusemide-induced changes in urinary PGE and kallikrein excretion were also the same as in normal subjects.

4. Impaired renal release of vasodilator prostaglandins in essential hypertension is likely to be secondary to the hypertension rather than an underlying factor in its development.
Lack of effect of Naloxone in a Moderate dosage on the Exercise-Induced Increase in Blood Pressure, Heart Rate, Plasma Catecholamines, Plasma Renin Activity and Plasma Aldosterone in Healthy Males
Authors: Bramnert Margareta , Bernt Hökfelt
Published: August 2015

1. There is evidence that opioid peptides influence blood pressure and heart rate in animals and man. In the present investigation the effect of naloxone on the exercise-induced increase in blood pressure, heart rate, plasma catecholamines, plasma renin activity (PRA) and plasma aldosterone was investigated in nine healthy men. A submaximal work test was performed on two occasions. The test consisted of ergometer bicycling for 10 min on 50% of maximal working capacity immediately followed by 10 min on 80% of maximal working capacity. Ten minutes before exercise the subjects received in a randomized manner a bolus dose of naloxone (10 μg/kg) or a corresponding volume of saline followed by a slow infusion (15 ml/h) of naloxone (5 μ h−1 kg−1) or saline, respectively.

2. After exercise systolic blood pressure, heart rate, plasma catecholamines, PRA and plasma aldosterone increased during both saline and naloxone infusion. The changes were similar in both studies.

3. Accordingly, opiate receptors sensitive to naloxone in a moderate dosage seem not to be involved in the cardiovascular response and the increase in plasma catecholamines, PRA and plasma aldosterone induced by exercise.
The effect of Intravenous Sodium Cromoglycate on the Bronchoconstriction Induced by Sulphur Dioxide Inhalation in Man
Authors: Allistone Anne , Collier J. G. , Davidson R. N. , Fuller R. W. , Richardson P. S.
Published: August 2015

1. Ten healthy subjects received, on separate occasions, intravenous infusions of 0.9% NaCl solution (saline) and of sodium cromoglycate given in a double-blind cross-over fashion.

2. After 20 min of infusion the specific airway conductance (sGaw) of each subject was measured in a body plethysmograph. The subject then breathed first a low (1-20 p.p.m.) and then a higher (4-40 p.p.m.) concentration of sulphur dioxide (SO2) for 2 min while the infusion continued. Measurements of sGaw were repeated after each inhalation of SO2.

3. Sodium cromoglycate infusion did not affect the sGaw measured before challenge with SO2.

4. During the infusion of sodium cromoglycate, the falls in sGaw in response to both concentrations of SO2 were significantly less than those which occurred during saline infusion.

5. Plasma concentrations of sodium cromoglycate were found to be 209 ± 22 nmol/l at the end of the drug infusion. This is about one-hundredth of lowest dose required to stabilize mast cells in vitro.

6. We conclude that sodium cromoglycate acted by a mechanism which did not involve mast cells. Other possible modes of action are discussed.
Effect of the Calcium Antagonist Verapamil on Human Leucocyte Sodium Transport in vitro
Authors: Gray H. H. , Poston L. , Johnson V. E. , Hilton P. J.
Published: August 2015

1. Sodium efflux rate constants and intracellular sodium were measured in leucocytes from healthy volunteers in the presence and absence of the calcium antagonist verapamil hydrochloride.

2. Verapamil stimulated sodium pump activity and this effect was dependent on the presence of external calcium.

3. Verapamil has been reported to reverse the abnormality of sodium transport seen in leucocytes from patients with essential hypertension and the present study demonstrates that sodium pump activity in leucocytes from control subjects is also stimulated by exposure to verapamil in vitro. This direct cellular effect appears to be due to the calcium antagonist properties of the drug.
The Causative Agent in Atrial Receptor Diuresis in the dog is a Low Molecular Weight, Lipophilic and Weakly Acidic Substance
Authors: Pither J. M. , Knapp M. F. , Gregory H. , Linden R. J.
Published: August 2015

1. Stimulation of atrial receptors by distension of a balloon in the left atrium of anaesthetized dogs results in a reflex diuresis mediated by a humoral agent of unknown identity.

2. In previous investigations, a substance was recovered in a low molecular weight fraction from Bio-Gel P-2 (100-1800 daltons) and shown to be related to the reflex diuresis.

3. In this investigation, the active Bio-Gel P-2 fraction was partitioned with ethyl acetate at pH 11.0, with subsequent partition of the aqueous phase with ethyl acetate at pH 7.4; the activity of the humoral agent was soluble in ethyl acetate at pH 7.4.

4. These investigations suggest that the humoral agent is a low molecular weight, lipophilic and weakly acidic substance.

5. The substance is not antidiuretic hormone (ADH) as vasopressin is insoluble in ethyl acetate at pH 7.4.
Splenic pooling of granulocytes
Authors: Peters A. M. , Saverymuttu S. H. , Keshavarzian A. , Bell R. N. , Lavender J. P.
Published: August 2015

1. The intrasplenic kinetics of granulocytes, isolated in plasma and labelled in plasma with 111In-tropolonate, have been studied in normal subjects, patients with negative studies for inflammatory disease and patients with positive studies, with the aim of identifying the nature of splenic activity seen after 111In-labelled granulocyte administration.

2. Up to 40 min after injection, 111In activity was visible only in major blood vessels, liver and spleen, with slight, abnormal activity visible in most of those with positive scans. The time courses of uptake of hepatic and splenic activity were different, with liver activity rapidly reaching a plateau and splenic activity increasing mono-exponentially to a plateau achieved between 20 and 40 min.

3. The clear difference between the shapes of the hepatic and splenic uptake curves and the magnitude of the splenic uptake rate constant indicated that splenic activity represented reversible uptake.

4. The application of deconvolution analysis to the blood and splenic time-activity curves generated a splenic retention (or washout) curve consistent with dynamic exchange of granulocytes between blood and spleen. The slope of this curve indicated an intrasplenic granulocyte transit time of 9.3 (±se 0.6) min.

5. Taking splenic activity to be reversible, comparison of the 111In signal from the spleen 40 min after injection of 111In-labelled granulocytes with that given from the spleen after the injection of 111In-labelled erythrocytes (relative to their respective blood levels) indicated that intrasplenic granulocyte transit time was 14.4 (±se 1.1) times that of erythrocytes. Based on actual erythrocyte time, this corresponds to a granulocyte transit time of 8.6-11.5 min, in close agreement with the estimate based on deconvolution analysis.

6. The reversibility of splenic 111In activity after labelled granulocyte injection was confirmed by observing falls in splenic activity between 40 min and 24 h and between 3 and 24 h, which were greater in patients with inflammatory disease than those without. Furthermore, a significant correlation was recorded between this fall and the fraction of the dose of 111In excreted in the faeces in patients with inflammatory bowel disease (IBD).

7. We conclude that the normal spleen contains a reservoir of granulocytes which is in dynamic equilibrium with circulating granulocytes (CGP). This pool therefore is a major component of the body's marginating granulocyte pool (MGP). The mean transit time of granulocytes through the spleen, about 10 min, is remarkably similar to that of platelets.
Selective dietary potassium depletion and acid-base equilibrium in the rat
Authors: Girard Pierre , Brun-Pascaud Monique , Paillard Michel
Published: August 2015

1. K+ depletion of two kinds was induced in two groups of rats by selective dietary restriction for up to 5 weeks. Complete metabolic studies for H+, K+, Na+ and Cl− were carried out daily during weeks 1, 3 and 5.

2. In control rats of group A (receiving K+ with sodium chloride), plasma pH (7.47) and HCO−3(25 mmol/l), as well TA (titratable acid) —- HCO−3 and NH+4 urinary excretion rates, were stable, while balances were nil for K+ and slightly positive for Cl−. In K+-deprived rats of group A receiving sodium chloride, a progressive metabolic alkalosis developed (plasma pH reached 7.57 and HCO−3 35.8 mmol/l by 5 weeks), and TA - HCO−3 and NH+4 urinary excretion rates were not different from controls. Plasma K+ fell progressively from 4.20 to 2.20 mmol/l, with negative K+ balance. Balances for Na+ and H2O were highly positive and plasma renin activity and aldosterone decreased by week 5. Hypochloraemia developed with positive Cl− balance.

3. In control rats of group B (receiving K+ with neutral sodium phosphate), a slight metabolic alkalosis developed, and TA - HCO−3 excretion rate was increased compared with control rats of group A. Balances were slightly negative for K+ and Cl−. In K+-deprived rats of group B receiving neutral sodium phosphate, a profound metabolic alkalosis developed (plasma pH reached 7.60 and HCO−3 42.6 mmol/l by 5 weeks), and TA-HCO−3 and NH+4 excretion rates were at no time different from those of control rats of group B. Plasma K+ fell progressively from 4.25 to 2.30 mmol/l, and K+ balance was more negative than that in control rats of group B. Hypochloraemia developed with a negative Cl− balance.

4. In both K+-restricted groups, a linear negative correlation was observed between plasma HCO−3 (or pH) and plasma K+. These results suggest that metabolic alkalosis does occur in sustained selective K+-depletion in rats. Metabolic alkalosis could be generated essentially by net transfer of H+ from extracellular fluid (ECF) into cells, probably in exchange for K+ in the reverse direction. Metabolic alkalosis could be maintained by an increase in tubular reabsorption of filtered HCO−3, probably via an enhanced Na+/H+ exchange in the proximal tubule in sodium chloride-loaded rats, which may account for the ECF volume expansion with low plasma renin activity and aldosterone, and via an enhanced Cl−/HCO−3 exchange in distal nephron in sodium phosphate-loaded rats.
An adenylate cyclase bioassay for parathyroid hormone: some clinical experiences
Authors: Seshadri M. S. , Chan Y. L. , Wilkinson M. R. , Mason R. S. , Posen S.
Published: August 2015

1. An adenylate cyclase bioassay for parathyroid hormone (PTH) was evaluated in peripheral sera of ten normal subjects, 15 patients with various types of hypoparathyroidism, nine patients with malignancy-associated hypercalcaemia and 60 patients with primary or secondary hyperparathyroidism. The lower limit of detectability was 150 pg/ml in terms of synthetic human PTH (1-34).

2. PTH-like bioactivity was not detected in normal subjects, in patients with surgical hypoparathyroidism, in patients with idiopathic hypoparathyroidism or in patients with malignancy-associated hypercalcaemia. Serum from one untreated pseudohypoparathyroid patient consistently contained PTH-like bioactivity.

3. Bioactivity was detected in sera from 50% of patients with primary or secondary hyperparathyroidism. In two patients with secondary hyperparathyroidism calcium infusions suppressed this activity within 5 min.

4. Both in primary and in secondary hyperparathyroidism there was a significant positive correlation between levels of PTH-like bioactivity, PTH immunoreactivity and the histological severity of the disease.
Arterial oxygen desaturation during treadmill and bicycle exercise in patients with chronic obstructive airways disease
Authors: Cockcroft A. , Beaumont A. , Adams L. , Guz A.
Published: August 2015

1. Nine men with severe chronic obstructive airways disease (COAD), known to desaturate on exercise, performed a 6 min self-paced walk on a treadmill, followed by a bicycle exercise with workloads adjusted to mimic the oxygen consumption achieved on the treadmill. During both exercises, ventilation, oxygen consumption, carbon dioxide production, Pao2, Paco2, pH and arterial lactate were measured and subjective breathlessness recorded.

2. A reasonable match of oxygen consumption between the two exercises was achieved. In all subjects Pao2 fell to a lower level during treadmill compared with bicycle exercise. Ventilation, carbon dioxide production and arterial lactate were higher during bicycle exercise. Subjective breathlessness was greater during bicycle exercise, in proportion to the higher ventilation on the bicycle.

3. The greater anaerobiosis occurring on the bicycle led to acidosis and an increased ventilation, minimizing the exercise fall in Pao2.

4. Bicycle testing may seriously underestimate exercise desaturation occurring during level walking in patients with severe COAD.
Effect of prolonged bile duct obstruction in the rat on hepatic transport of bilirubin
Authors: Kountouras Jannis , Scheuer Peter J. , Billing Barbara H.
Published: August 2015

1. In order to investigate the effect of extra-hepatic biliary obstruction on bilirubin transport, bile flow was re-established after 5, 10, 15 and 28 days when the mean (±sem) plasma bilirubin concentrations of the four groups of five rats were 226 ± 17.9, 201 ± 22.4, 178 ± 8.1 and 145 ± 3.8 μmol/l, respectively.

2. After 12 h of bile drainage in the conscious animal, the mean plasma bilirubin concentrations of the four groups had decreased by 88, 86, 73 and 46%, respectively.

3. The bile flow rate increased with the duration of the obstruction and was maximal in the 28 day obstructed rats, although the bilirubin output in these animals was significantly less than in the other groups.

4. Histological evidence of biliary obstruction was apparent in the livers of the 5 and 10 day obstructed animals. After 15 days of obstruction cirrhosis developed.

5. In conclusion, the disposal of endogenous bilirubin in the bile duct obstructed rat appears to be influenced by the development of cirrhosis.
Sodium pentosan polysulphate as a polyanionic inhibitor of calcium oxalate crystallization in vitro and in vivo
Authors: Norman R. W. , Scurr D. S. , Robertson W. G. , Peacock M.
Published: August 2015

1. Studies in vitro showed that sodium pentosan polysulphate (SPP) is an active inhibitor of calcium oxalate crystal growth and agglomeration and that it acts by increasing the negative zeta potential on the surface of calcium oxalate crystals.

2. Oral administration to human subjects resulted in an increase in the negative zeta potential, which is consistent with an increase in the polyanionic inhibitory activity of urine. SPP may offer a novel approach to the medical management of recurrent calcium oxalate stone disease.
Calmodulin levels in hypertensive rats
Authors: Higaki J. , Ogihara T. , Kumahara Y. , Bravo E. L.
Published: August 2015

1. Intracellular calmodulin levels were measured by direct radioimmunoassay in spontaneously hypertensive rats (SHR) and Wistar—Kyoto rats (WKY).

2. Decreased calmodulin levels were demonstrated in the brain, heart, aorta and kidney of spontaneously hypertensive rats compared with those in Wistar—Kyoto rats.

3. Calmodulin levels in the brain were also decreased in deoxycorticosterone acetate (DOCA)-salt rats, but not changed significantly in the heart, aorta and kidney compared with those in Wistar—Kyoto rats.

4. These findings suggest that intracellular calcium-dependent regulatory systems are genetically disrupted in spontaneously hypertensive rats, but this is probably not an important factor in the development of hypertension.
Human mast cells recovered by bronchoalveolar lavage: their morphology, histamine release and the effects of sodium cromoglycate
Authors: Flint K. C. , Leung K. B. P. , Pearce F. L. , Hudspith B. N. , Brostoff J. , Johnson N. McI.
Published: August 2015

1. Mast cells make up between 0.5 and 3% (mean 1.35%) of total cells recovered by bronchoalveolar lavage (BAL).

2. The majority of these cells have the morphological characteristics of mucosal mast cells in that they fail to stain in the alcian blue-safranin reaction after fixation in formol-saline but stain well after fixation in Carnoy's solution. Cells staining with berberine sulphate were seen in only four of the 26 lavages.

3. BAL cells released histamine in response to anti-human immunoglobulin E (IgE) in a dose-dependent manner that was optimal at a dilution of anti-IgE of 1:100. Maximum release was obtained by 2 min.

4. Histamine release was completely inhibited by a combination of 2-deoxyglucose (5 mmol/l) and antimycin A (1 μmol/l).

5. Disodium cromoglycate (DSCG) significantly inhibited this histamine release at 1 mmol/l (P<0.02), 100 μmol/l (P<0.002) and 10 μmol/l (P<0.003), with maximum inhibition of 50.1% at 10 μmol/l.
Effects of dietary fish oil supplementation on the fatty acid composition of the human platelet membrane: demonstration of selectivity in the incorporation of eicosapentaenoic acid into membrane phospholipid pools
Authors: Galloway John H. , Cartwright Ian J. , Woodcock Barrie E. , Greaves Michael , Graham R. , Russell G. , Preston F. Eric
Published: August 2015

1. The fatty acid composition of membrane phospholipids of stimulated and unstimulated platelets was studied in six normal volunteers given a daily dietary supplement of a fish oil rich in eicosapentaenoic acid (EPA) for 4 weeks. The supplement was equivalent to 1.8 g of EPA daily. Thromboxane synthesis and platelet aggregation responses to sodium arachidonate, thrombin and the ionophore A23187 were also investigated.

2. A marked increase in the relative EPA content of phosphatidylcholine (PC) and phosphatidylethanolamine (PE) was noted after 2 and 4 weeks fish oil supplementation. However, there was no incorporation into phosphatidylinositol (PI) or phosphatidylserine (PS). The relative arachidonic acid (AA) content of PC and PE was significantly reduced at 2 and 4 weeks but that of PI and PS remained unchanged. Significant reductions in the relative linoleic acid content of total phospholipids, PC and PE were also noted.

3. Stimulation of platelets obtained after 4 weeks fish oil supplementation by thrombin and A23187 was associated with a marked reduction in the AA content of PI and a minor reduction in that of PE. There was no change in the relative proportions of EPA in PI, PS, PC or PE after stimulation. Throughout the study there were no significant changes in platelet aggregation responses or in platelet thromboxane production.

4. Our results indicate that the incorporation of EPA into the platelet membrane phospholipids is selective and that if PI is the major source of AA for platelet prostaglandin biosynthesis then the reported beneficial effects of EPA on haemostasis cannot be explained on the basis of its incorporation into and mobilization from the platelet membrane phospholipid pool.
Mass and composition of the fat-free tissues of patients with weight-loss
Authors: Burkinshaw L. , Morgan D. B.
Published: August 2015

1. An estimate of the mass of fat-free tissue in the body can be calculated from body weight and skinfold thickness; this estimate is called the ‘fat-free mass'. Total body potassium and nitrogen are alternative estimates. Factor analysis of data for healthy subjects has defined relationships between the true values of these three quantities and estimated the random component of the variance of each, i.e. the component independent of variations in the mass of fat-free tissue. The results indicated that all three were reliable measures of the mass of fat-free tissue. However, it is not known whether these findings are valid for patients who have lost weight.

2. We have measured the same three quantities in 104 wasted patients with heart disease or disorders of the gastrointestinal tract. The patients’ mean values were significantly less than corresponding values for healthy volunteers. The patients had a mean ratio of total body nitrogen to fat-free mass similar to that of healthy subjects, but lower mean ratios of potassium to fat-free mass and nitrogen. These findings suggest that the potassium content of the patients’ fat-free tissues was abnormally low.

3. Factor analysis of the patients’ data gave relationships between the true values of the three quantities similar to those for healthy subjects; however, total body potassium was 100-300 mmol lower in patients than in healthy subjects with the same fat-free mass or total body nitrogen.

4. Factor analysis also showed that the random components of variance of fat-free mass and total body nitrogen were similar to those in healthy subjects. Therefore, in the patients as in healthy subjects, fat-free mass was as valid a measure of fat-free tissue as the more complex measurement of total body nitrogen. The random component of total body potassium was twice as big as in healthy subjects; however, it formed no greater a proportion of total variance than did the random components of the other two quantities.

5. Total body nitrogen, and hence body protein, could be estimated from measured fat-free mass with a standard error of approximately 136 g (compared with 139 g for healthy individuals), and from total body potassium with a standard error of 129 g (compared with 91 g in healthy subjects).
Impaired baroreflex sensitivity in the aetiology of salt hypertension in the rabbit
Authors: Weinstock Marta , Schorer-Apelbaum Donna
Published: August 2015

1. This study was designed to see whether normotensive rabbits with an impairment in baroreflex control of heart rate due to genetic factors are more susceptible to high salt or deoxycorticosterone acetate (DOCA)-salt hypertension. The baroreflex sensitivity of 27 conscious rabbits was assessed by both the ‘steady-state’ and ‘ramp’ methods in response to injections of phenylephrine (2.5-30 μg/kg).

2. Animals with differing baroreflex sensitivities were then given 4 weeks treatment with 8% NaCl and 1.3% KCl in food (treatment A), or DOCA (25 mg pellet, subcutaneously) with 0.5% NaCl and 0.13% KCl in drinking water (treatment B). A third group were maintained on a regular diet of food and water (controls).

3. A highly significant negative correlation (r = 0.91, P < 0.01) was found between the increase in mean arterial pressure (MAP) produced either by treatment A or treatment B and the baroreflex sensitivity before treatment. There was no significant correlation between the increase in MAP and (a) initial MAP; (b) increase in body weight; (c) serum K+ after treatment; (d) baroreflex sensitivity before treatment, when assessed by the ‘ramp’ method.

4. It is concluded that animals with low baroreflex sensitivity due to a reduced ability to suppress cardiac sympathetic activity in response to a pressor stimulus, are more likely to develop hypertension as a result of salt loading. It remains to be determined whether the susceptibility to salt of rabbits with lower baroreflex sensitivity is also associated with a difference in the renal excretion of Na+ ions.
Salt-induced hypertension in the ‘Sabra’ rat strain: influence of nifedipine treatment
Authors: Garthoff Bernward , Ebsen Wolfgang , Luckhaus Georg , Kazda Stanislav , Ben-Ishay Drori
Published: August 2015

1. The effects of chronic dietary salt-loading and nifedipine therapy on hypertension-prone (SBH), -resistant (SBN) and parental (SB) Sabra rats were investigated. Salt diet for 12 weeks resulted in a sustained hypertension and heart hypertrophy only in SBH.

2. Nifedipine therapy (300 p.p.m. = 300 mg/kg of food) introduced after week 7 on a salt diet, achieved small changes in salt-loaded SBN and SB rats, but resulted in a marked decrease in blood pressure in SBH rats within 1 week and in a regression of cardiac hypertrophy.

3. Plasma renin activity rose slightly in nifedipine treated SB and SBN rats, but decreased significantly in treated SBH rats.

4. Histopathological investigations revealed hypertensive vasculopathy in three out of nine untreated SBH rats, whereas there were no morphological changes in the treated rats.
Cation transport functions in vitro in patients with untreated essential hypertension: a comparison of erythrocytes and leucocytes
Authors: Boon N. A. , Harper C. , Aronson J. K. , Grahame-Smith D. G.
Published: August 2015

1. We have measured intracellular sodium concentrations and specific 3H-labelled glycoside binding characteristics in the erythrocytes and leucocytes of patients with untreated essential hypertension, and have compared the results with those in well-matched normotensive control subjects.

2. Intracellular sodium concentrations were increased in the leucocytes, but not in the erythrocytes, of patients with untreated essential hypertension.

3. There were no differences in the 3H-labelled glycoside binding characteristics of either the erythrocytes or the leucocytes of hypertensive and normotensive subjects.

4. There was no difference in the ability of plasma samples from hypertensive and normotensive subjects to inhibit the binding of [3H]-ouabain to intact leucocytes from normotensive subjects.

5. These findings are not consistent with the presence of increased concentrations of a substance which behaves like a cardiac glycoside in the circulation of patients with untreated essential hypertension.
Adrenaline and ion flux in isolated human leucocytes
Authors: Baron D. N. , Green Rachel J. , Khan F. A.
Published: August 2015

1. Hypokalaemia may be produced in man by intravenous adrenaline infusion, or as a result of pathological disturbances which have led to a high plasma adrenaline concentration.

2. With isolated human leucocytes used as a cellular model, adrenaline at concentrations at and above 9 nmol/l increases the influx of rubidium (a model for potassium flux) into cells, with a simultaneous efflux of sodium. There is no effect on Na+, K+-ATPase activity in lysed leucocytes.

3. Use of the adrenoceptor blockers timolol and atenolol shows that the demonstrated effect of adrenaline on coupled active transport of ions is mediated by β2-adrenoceptors.
Human Tamm-Horsfall glycoprotein: urinary and plasma levels in normal subjects and patients with renal disease determined by a fully validated radioimmunoassay
Authors: Thornley Carolyn , Dawnay Anne , Cattell W. R.
Published: August 2015

1. A recently developed, simple and sensitive radioimmunoassay has been used to examine 24 h excretion and plasma levels of Tamm-Horsfall glycoprotein (THG) in normal subjects, stone formers and patients with stable chronic renal disease.

2. In normal subjects THG excretion ranged from 22 to 66 mg/24 h, with no sex difference and no correlation with creatinine clearance or body surface area. There was no correlation between 24 h THG excretion and urine volume, pH or osmolality, excretion of Na+, K+ or Ca2+ or free-water clearance. There was a small significant correlation between plasma THG concentration and urinary THG excretion.

3. A good correlation was obtained between the THG/creatinine ratio in 24 h and random samples. This made possible the use of random samples to establish a reference range for THG excretion of 0.15-0.50 μg/ml of creatinine clearance which did not depend on sex or age.

4. The excretion rate of THG in stone formers was generally within the reference range. It was not significantly different in those who were hypercalciuric or in those taking thiazides.

5. In patients with chronic renal disease there was a good correlation between 24 hTHG excretion, plasma THG concentration and creatinine clearance. The range of excretion of THG per ml of creatinine clearance was greater than in normal subjects, independent of the type of renal disease and unrelated to proteinuria.

6. In patients with glomerulonephritis the excretion of THG per ml of creatinine clearance was significantly higher in those with well-preserved tubules compared with those with tubular atrophy.
Antidiuretic hormone response to volume depletion in diabetic patients with cardiac autonomic dysfunction
Authors: Grimaldi André , Pruszczynski Wojciech , Thervet Francis , Ardaillou Raymond
Published: August 2015

1. Thirty-three insulin-dependent diabetic patients were separated into two groups from the results of three different tests for cardiac vagal neuropathy: heart rate response to deep breathing, Valsalva manoeuvre and heart rate response to postural change. Seventeen patients were considered as without ('intact’ patients) and 16 as with ('denervated’ patients) cardiac autonomic dysfunction. One patient with a transplanted heart was also studied.

2. Plasma antidiuretic hormone (ADH), plasma aldosterone and plasma renin activity (PRA) were measured immediately before and 60 min after intravenous administration of frusemide and passage from lying to standing. The kinetics of hormonal responses were analysed more precisely (five blood collections) in six patients of each group who were studied again. Heart rate and blood pressure were recorded before each blood collection.

3. Volume depletion estimated from the rise in plasma protein (+ 11.9 and + 12.2% in ‘denervated’ and ‘intact’ patients respectively) and heart rate response (+ 10.6 and + 14.7%) were similar in both groups. Mean blood pressure was unchanged in the ‘intact’ patients whereas it fell in the ‘denervated’ patients (−13.5%). PRA (+ 161.5 and + 231.2% in ‘denervated’ and ‘intact’ patients respectively) and plasma aldosterone (+ 318.2 and 279%) increased in both groups whereas plasma ADH was stimulated only in ‘intact’ patients (+ 55.3%). The failure of ADH to respond significantly to the volume stimulus in ‘denervated’ patients was confirmed by the results of the time-course study. Plasma ADH remained at the same levels in ‘denervated’ patients whereas it increased significantly (+ 82.4%) in ‘intact’ patients. There was no ADH response in the transplanted patient.

4. These results suggest that, in humans, cardiac receptors and vagal pathways play a role in ADH response to volume depletion.
Superoxide radicals, immunodeficiency and xanthine oxidase activity: man is not a mouse!
Authors: Simmonds H. A. , Goday A. , Morris G. S.
Published: August 2015

1. The importance of intact adenosine deaminase (ADA) activity in the generation of superoxide anion by xanthine oxidase has been disputed in studies using human neutrophils or mouse macrophages. The latter demonstrated a positive correlation between ADA activity and superoxide production during phagocytosis. The immunodeficiency in inherited ADA deficiency was related to a defect in this process.

2. Since there is considerable interspecies variation in the tissue distribution of xanthine oxidase, the metabolism of [8-14C]deoxyadenosine (dAR), the toxic metabolite which accumulates in inherited ADA deficiency, was investigated in human peritoneal macrophages.

3. Evaluation of the distribution of radiolabel in both cell and medium demonstrated that human macrophages with intact ADA metabolize dAR under physiological conditions to deoxyinosine and hypoxanthine exclusively. The hypoxanthine is further metabolized within the cell to ATP and GTP, via IMP.

4. No xanthine or uric acid could be detected, confirming that in human macrophages xanthine oxidase activity is insignificant, as it is in most other human cells and tissues, except liver and intestinal mucosa. Thus production of superoxide radicals in such cells via this route would be impossible, and consequently unaffected either by ADA deficiency or the xanthine oxidase inhibitor allopurinol.