bluuebunny/crossref_metadata_2025 huggingface dataset:
Factors affecting Potassium Balance During Frusemide Administration
Authors: Wilcox Christopher S. , Mitch William E. , Kelly Ralph A. , Friedman Paul A. , Souney Paul F. , Rayment Carolyn M. , Meyer Timothy W. , Skorecki Karl L.
Published: August 2015

1. We investigated the effects of Na+ intake, the renin-angiotensin-aldosterone system and antidiuretic hormone (ADH) on K+ balance during 3 days of frusemide administration to six normal subjects. Subjects received 40 mg of frusemide for 3 days during three different protocols: Na+ intake 270 mmol/day (high salt); Na+ intake 20 mmol/day to stimulate the renin-angiotensin-aldosterone system (low salt); Na+ intake 270 mmol/day plus captopril (25 mg/6 h) to prevent activation of the renin-angiotensin-aldosterone system. In a fourth protocol, a water load was given during high salt intake to prevent ADH release and then frusemide was given.

2. During high salt intake, frusemide increased K+ excretion (UKV) over 3 h, but the loss was counterbalanced by subsequent renal K+ retention so that daily K+ balance was neutral.

3. During low salt intake, the magnitude of the acute kaliuresis following the first dose of frusemide and the slope of the linear relationship between UKV and the log of frusemide excretion were increased compared with that found during the high salt intake. In addition, low salt intake abolished the compensatory renal retention of K+ after frusemide and cumulative K+ balance over 3 days of diuretic administration was uniformly negative (−86 ± 7 mmol/3 days; P < 0.001).

4. Captopril abolished the rise in plasma aldosterone concentration induced by frusemide. The acute kaliuresis after frusemide was unchanged compared with that observed during high salt intake. The compensatory reduction in UKV occurring after the diuretic was slightly potentiated. In fact, captopril given without the diuretic induced a small positive K+ balance.

5. When a water load was given concurrently with frusemide, the acute kaliuresis was >30% lower compared with that seen with frusemide alone, even though the natriuretic response was unchanged.

6. We conclude that: (a) K+ balance is maintained when frusemide is given during liberal Na+ intake because acute K+ losses are offset by subsequent renal K+ retention; (b) this compensatory K+ retention can be inhibited by aldosterone release which could account for the negative K+ balance seen during salt restriction; (c) the short-term kaliuretic response to frusemide is augmented by release of both ADH and aldosterone whereas changes in K+ balance over 3 days of frusemide are dependent on plasma aldosterone concentration.
Changes in Gastric Emptying Rates with Age
Authors: Horowitz Michael , Maddern Guy J. , Chatterton Barry E. , Collins Peter J. , Harding Philip E. , Shearman David J. C.
Published: August 2015

1. A dual isotope technique which measures simultaneously the emptying of solids and liquids by the stomach was used to study gastric emptying in 35 subjects in the age range 21-84 years, who were all fit, mobile volunteers and were not taking any drugs.

2. Solid and liquid emptying were significantly slower in older subjects, but this finding is unlikely to be of clinical significance because the changes were small and emptying rates were usually within the normal range for younger subjects.
Inhibitor Binding Assay of rat Serum Angiotensin Converting Enzyme
Authors: Tikkanen Ilkka , Fyhrquist Frej , Forslund Terje
Published: August 2015

1. Based on a specific binding of labelled inhibitor to the enzyme active centre, a new principle of enzyme assay, inhibitor binding assay (IBA), was developed and applied to measurement of rat serum angiotensin converting enzyme (ACE).

2. Serum diluted 1:50 was incubated with 125I-labelled ACE inhibitor, 351A, at pH 7.0, 37°C, for 2 h. Inhibitor bound to ACE was separated with coated charcoal and results were calculated from a standard curve.

3. The advantages offered by the novel inhibitor binding assay include simplicity, specificity, absence of interference by other enzymes or immunological cross-reactions, and great sensitivity enabling measurement of ACE in concentrations less than 0.1 units/ml.

4. This principle of enzyme assay will not only have potential new applications for research involving ACE but may also be extended to other enzymes.
Ascending Brain-Stem Noradrenergic Pathways Modulate the Renin Response to Haemorrhage
Authors: Lightman S. L. , Todd K. , Everitt B. J. , Brown M. J. , Causon R. C.
Published: August 2015

1. Ventral noradrenergic projections (VNAB) from lateral tegmental (A1, A2) and dorsal noradrenergic projections (DNAB) from the coeruleal (A6) as well as A1 cell groups in the brain-stem of the rat were lesioned by intracerebral injection of 6-hydroxydopamine.

2. A marked increase in plasma renin activity and adrenaline concentrations followed haemorrhage (0.5 ml/100 g body weight) in the sham-operated rats. VNAB-lesioned rats showed a similar response to the sham-operated controls, but in DNAB-lesioned animals the rise of plasma renin was markedly attenuated.
The Basal Levels of Active and Inactive Plasma Renin Concentration in Infancy and Childhood
Authors: Fiselier T. , Derkx F. , Monnens L. , Van Munster P. , Peer P. , Schalekamp M.
Published: August 2015

1. Basal plasma renin activity, active and inactive plasma renin concentration were measured in 89 healthy recumbent children aged between 1 week and 16 years.

2. A significant (P<0.001) age-related decrease for active (r = −0.60), inactive (r = −0.59) and total renin concentration (r = −0.66) was observed.

3. After correction for the influence of age, active renin concentration correlated with plasma renin activity (r = 0.81), but not with inactive renin concentration (r = 0.18).

4. The proportions of active and inactive renin were not related to age, and the overall percentage of inactive renin was 79%.
Differences in the Effect of Mediastinal Radiotherapy on Lung Function and the Ventilatory Response to Exercise
Authors: Jones P. W. , Al-Hillawi A. , Wakefield J. M. , Johnson N. McI. , Jelliffe A. M.
Published: August 2015

1. To examine the effect of lung inflammation on lung volumes and carbon monoxide transfer and their relationship to the ventilatory and gas exchange responses to exercise, a prospective study was performed in patients having Hodgkin's disease, with no evidence of intrathoracic involvement, who received prophylactic mantle-field radiotherapy to the chest.

2. From 6 weeks to 6 months from the start of therapy, vital capacity (FVC) was on average 10.4% lower than during the baseline period and the total transfer of carbon monoxide (TLCO) was 10.5% lower. Minute ventilation (V̇E) at any given work load during an incremental exercise test was on average 10.5% higher than baseline. The stimulation of ventilation after radiotherapy was present at all work rates, but greater at high work rates.

3. A number of other changes in the ventilatory and gas exchange responses to exercise were also seen. Most of these lay outside the range of variability observed in a group of normal subjects tested concurrently with the patients.

4. There was a poor, but statistically significant, positive correlation between reduction in FVC and increase in V̇E after radiotherapy and between reduction in carbon monoxide transfer and increase in V̇E.

5. A significant correlation between reduction in FVC and change in respiratory rate was also seen after radiotherapy, together with a significant inverse correlation between increase in respiratory rate and fall in tidal volume.

6. The ratio of V̇E to oxygen consumption, the ventilatory equivalent for oxygen, was calculated at each work rate. There was a negative correlation between the mean increase in this parameter, averaged over all work rates, and the reduction in FVC and TLCO, i.e. the greatest stimulation of breathing relative to metabolic demand occurred in those patients with the least change in lung volume.

7. In the period after 6 months lung volumes and carbon monoxide transfer fell further, or remained the same, but V̇E returned towards pretreatment levels.

8. It is suggested that changes in ventilatory response to work after lung inflammation, are the result of a balance between an increased drive to breathe and changes in the mechanical properties of the lungs.
Correlation between Platelet Behaviour and Cold-Induced Vasoconstriction in Man, and the Effects of Epoprostenol Infusion
Authors: Cowley A. J. , Stainer Karen , Cockbill S. , Heptinstall S.
Published: August 2015

1. Drugs that cause vasodilatation tend to inhibit platelet behaviour whereas compounds that cause vasoconstriction stimulate platelet behaviour. Thus there appears to be a similarity between platelet behaviour and vascular tone. To investigate this relationship we have compared the maximum vasoconstrictor response in the forearm induced by cold stimulation with some aspects of platelet behaviour.

2. In 26 normal volunteers there was a close correlation between the maximum vasoconstrictor response to cold and the threshold concentration of sodium arachidonate that was needed to induce platelets from each individual to aggregate and to undergo a release reaction (r = 0.774, P<0.001).

3. Infusion of epoprostenol (prostacyclin) in five volunteers altered both the maximum vasoconstrictor response to cold and the threshold concentration of sodium arachidonate needed to induce platelet aggregation in a manner parallel to this relationship.
Uptake of a Series of Neutral Dipeptides Including l-Alanyl-l-Alanine, Glycylglycine and Glycylsarcosine by Hamster Jejunum in Vitro
Authors: Matthews D. M. , Burston D.
Published: August 2015

1. This paper is the last of a set reporting an investigation of the kinetics of jejunal uptake and inhibitory ability of a series of neutral dipeptides, glycylglycine, l-ananyl-l-alanine, l-valyl-l-valine and l-leucyl-l-leucine, with progressively longer and more lipophilic side chains.

2. The results suggested that at pH 5, uptake of l-alanyl-l-alanine, like that of l-valyl-l-valine and l-leucyl-l-leucine, was the result of two processes, uptake of intact peptide and uptake of free amino acid released extracellularly. On the other hand, uptake of glycylglycine was entirely in the form of intact peptide. In contrast to uptake of l-valyl-l-valine and l-leucyl-l-leucine, the proportion of intact l-alanyl-l-alanine taken up by mediated transport was greatest at the lowest concentration studied and smallest at the highest concentration.

3. Taking the series of results as a whole, whereas the corresponding series of amino acids, glycine, l-alanine, l-valine and l-leucine, showed a progressive increase in apparent affinity for uptake and a decrease in Vmax., we could find no such regular progression with the peptides.

4. The results of work on inhibition of uptake of one dipeptide by another were unexpectedly complex. Examples were the very powerful inhibitory effect of l-valyl-l-valine on uptake of glycylsarcosine, not suggested by the Kt of the former peptide, and the failure of glycylsarcosine to cause complete inhibition of uptake of l-alanyl-l-alanine and l-leucyl-l-leucine, though it could completely inhibit uptake of l-valyl-l-valine. There may be more than one uptake system for intact peptides, but we cannot yet suggest an explanation for all the results on inhibitions of uptake.
Thyroid Status in Patients after Acute Myocardial Infarction
Authors: Franklyn J. A. , Gammage M. D. , Ramsden D. B. , Sheppard M. C.
Published: August 2015

1. Subjects followed serially after acute myocardial infarction demonstrated a rapid and sustained fall in serum total tri-iodothyronine (T3) concentration and a rise in reverse tri-iodothyronine (rT3) concentration. There was a transient fall in total thyroxine (T4) concentration.

2. Thyroxine binding globulin (TBG) levels were unchanged after acute myocardial infarction but prolonged falls were observed in thyroxine binding prealbumin (TBPA) and albumin concentrations.

3. In contrast to the fall in total T4, both measured and calculated free T4 concentrations were unchanged but measured and calculated free T3 concentrations fell as did total T3.

4. Despite the observed fall in T3, basal thyrotrophin (TSH) concentrations did not rise.

5. The reduction in circulating T3 levels after acute myocardial infarction suggests that a hypothyroid state exists. Until tissue thyroid status can be assessed directly, however, this conclusion must remain in doubt.
Comparison of Atrial Pacing and the Cold Pressor Test in Patients with Angina Pectoris
Authors: Emanuelsson H. , Caidahl K. , Hjalmarson Å. , Holmberg S. , Svensson S.-E. , Waagstein F. , Waldenström A.
Published: August 2015

1. A haemodynamic and myocardial metabolic study was performed to compare effects of maximal atrial pacing and the cold pressor test (CPT) in patients with angina pectoris. Twelve patients (group I) had angiographically severe coronary artery disease, while 16 patients (group II) had normal coronary angiograms.

2. At maximal pacing, angina developed in all patients in group I, and myocardial lactate production was found in eight of 12 patients. In group II, 12 out of 16 patients experienced chest pain, but only two patients had myocardial lactate production. Neither angina nor myocardial lactate production was present in any patient in either group during CPT.

3. Coronary sinus flow increased and coronary vascular resistance decreased significantly in both groups at maximal pacing (P<0.001). At CPT, coronary flow decreased (P<0.05) and coronary resistance increased (P<0.001) in group I, while individual response was more variable in group II.

4. In conclusion, maximal pacing was a more effective method of provocation of angina pectoris than CPT. The reactions of coronary sinus flow and coronary vascular resistance were different in group I than in group II. However, because of the variability of response in patients with normal coronary arteries, CPT cannot be used to distinguish patients with coronary artery disease from patients with no such disease.
Prostacyclin and Thromboxane in Non-Insulin Dependent Diabetes: The Chlorpropamide Alcohol Flush Reaction Revisited
Authors: Johnston Colin , Carey Frank , Forder Robert A. , Haworth Duncan
Published: August 2015

1. Levels of immunoreactive 6-oxo-prostaglandin F1α (6-oxo-PGF1α) and thromboxane B2 (TXB2) were measured in peripheral venous plasma in a group of volunteers and non-insulin dependent diabetic patients (NIDDS). Levels of these eicosanoids were close to the limit of sensitivity of the radioimmunoassays and consequently data are reported as maximal values. Basal plasma levels of 6-oxo-PGF1α did not exceed 5 pg/ml in either group and maximal levels of immunoreactive TXB2 were 125 ± 14 and 128 ± 8 pg/ml for volunteers and NIDDS respectively.

2. Attempts to elicit peripheral vascular prostacyclin biosynthesis in volunteers by using forearm ischaemia produced no increase in plasma 6-oxo-PGF1α levels. Measurement of the combined plasma levels of 6-oxo-PGF1α, 13,14-dihydro-6-oxo-PGF1α, 13,14-dihydro-6,15-dioxo-PGF1α and 6-oxo-PGE1 indicated that these were also low (less than 5 pg/ml) and that failure to demonstrate increased 6-oxo-PGF1α levels was unlikely to have arisen from metabolism of prostacyclin to one or more of these metabolites.

3. Measurement of 6-oxo-PGF1α and TXB2 in peripheral venous plasma before and during chloropropamide alcohol flushing (CPAF) did not provide evidence for a role for these eicosanoids in the etiology of this phenomenon.

4. These findings point to the need for a reappraisal of studies that have described altered plasma levels of 6-oxo-PGF1α and TXB2 in CPAF and other pathophysiological conditions in man.
Dexamethasone Inhibits the Production of Thromboxane B2 and Leukotriene B4 by Human Alveolar and Peritoneal Macrophages in Culture
Authors: Fuller Richard W. , Kelsey Christopher R. , Cole Peter J. , Dollery Colin T. , MacDermot John
Published: August 2015

1. Cultured human alveolar and peritoneal macrophages have been shown to release thromboxane B2 and leukotriene B4.

2. The release was facilitated by stimulation of the macrophages with opsonized zymosan A (1.2 mg/ml).

3. The release was inhibited in a concentration-dependent manner by incubation of the cells with dexamethasone (1 nmol/l to 1 μmol/l).
Gas Transfer for Carbon Monoxide in Polycythaemia Secondary to Hypoxic Lung Disease
Authors: Wedzicha J. A. , Cotter F. E. , Wallis P. J. W. , Newland A. C. , Empey D. W.
Published: August 2015

1. The transfer factor for carbon monoxide and its subdivisions, the membrane diffusing capacity (Dm) and the pulmonary capillary blood volume (Vc), were measured in 16 patients with polycythaemia secondary to chronic hypoxic lung disease and in ten hypoxic non-polycythaemic control subjects.

2. The mean pulmonary capillary blood volume was significantly lower in the polycythaemic patients (31.6 ml, sd 11.2) compared with the control group (65.2 ml, sd 22.5) (P<0.001).

3. Erythrapheresis, as a method of isovolaemic haemodilution, was performed in 15 of the polycythaemic patients. The mean packed cell volume fell from 58 (sd 5)% to 47 (sd 5)% after treatment, with significant reductions in blood viscosity at both high and lower shear rates (P<0.001).

4. The mean pulmonary capillary blood volume increased from 32.3 ml (sd 11.3) before treatment to 48.7 ml (sd 18.7) after erythrapheresis (P<0.01), with no significant change in membrane diffusing capacity.

5. The rise in pulmonary capillary blood volume is another potential physiological advantage of the reduction of packed cell volume in patients with polycythaemia secondary to hypoxic lung disease.
Enhancement of the Urinary Excretion of Non-Sulphated and Sulphated Radioactive Bile Acids by Sodium Acetate in the Bile Duct Obstructed Rat
Authors: Chitranukroh A. , Taggart G. , Billing B. H.
Published: August 2015

1. The renal clearances of [14C]glycocholate, [14C]taurocholate and [3H]glycochenodeoxycholate-3-sulphate were determined in bile duct obstructed rats.

2. Comparisons of the bile acid clearances with glomerular filtration rates (GFR) indicate that most of the filtered bile acids are reabsorbed.

3. Inhibition studies with p-aminohippurate (PAH) and probenecid suggest that a proportion of the bile acids in urine is secreted.

4. Attempts were made to increase the renal clearance of the bile acids by the administration of pharmacological agents.

5. An infusion of sodium acetate (0.3 mol/l) increased the clearance of the radioactive bile acids and augmented the urinary excretion of endogenous 3α-hydroxy bile acids and reduced their concentration in plasma.
Plasma Catecholamine Responses to Change of Posture in Alcoholics during Withdrawal and after Continued Abstinence from Alcohol
Authors: Eisenhofer G. , Whiteside E. A. , Johnson R. H.
Published: August 2015

1. Plasma catecholamine, blood pressure and heart rate responses to standing were measured in ten alcoholics during withdrawal, ten alcoholics after 2–7 weeks of abstinence from alcohol, six abstinent alcoholics with orthostatic hypotension and ten normal control subjects.

2. Withdrawing alcoholics had supine and standing heart rates and plasma noradrenaline and adrenaline concentrations that were higher than in abstinent alcoholics or control subjects. Supine blood pressures were also higher in withdrawing alcoholics than in abstinent alcoholics or control subjects, but on standing blood pressures in withdrawing alcoholics fell, four patients having a fall of more than 30/5 mmHg.

3. Abstinent alcoholics without orthostatic hypotension had higher basal and standing concentrations of noradrenaline than control subjects but normal heart rates and adrenaline concentrations.

4. Abstinent alcoholics with orthostatic hypotension showed a wide range of basal plasma noradrenaline concentrations and were found to have variable plasma noradrenaline responses to standing, three subjects having normal responses and three subjects having no or little increase in plasma noradrenaline on standing.

5. It is concluded that alcohol withdrawal is associated with increased sympathetic nervous activity, as reflected by raised supine and standing plasma concentrations of catecholamines, and that even after 2–7 weeks of abstinence from alcohol plasma noradrenaline concentrations may be higher than in control subjects. Despite increased sympathetic nervous responses to standing, alcoholics during withdrawal have impaired blood pressure control and some may exhibit orthostatic hypotension. Orthostatic hypotension may also be observed in alcoholics during continuing abstinence from alcohol; in some of these patients failure of reflex noradrenaline release in response to standing may contribute to orthostatic hypotension.
Selective Inhibition of Renal Thromboxane Biosynthesis Increased Sodium Excretion Rate in Normal and Saline-Loaded Rats
Authors: Papanicolaou N. , Gkika E.-L. , Gkikas G. , Bariety J.
Published: August 2015

1. The excretion rates of renal thromboxane B2 (TXB2) and 6-ketoPGF1α, the stable chemical metabolites of thromboxane A2(TXA2) and prostaglandin I2 (PGI2) respectively, PGE2 and sodium were determined in normal and saline-loaded rats treated with the thromboxane synthetase inhibitor imidazole.

2. In normal rats the administration of imidazole in doses which did not affect renal 6-keto-PGF1α and PGE2 excretion but selectively inhibited renal TXB2 excretion, significantly increased the sodium excretion rate.

3. Volume expansion with saline increased renal PGE2 and 6-ketoPGF1α excretion but did not alter renal TXB2 excretion. The increase in renal prostaglandin excretion was accompanied by an increased sodium excretion rate.

4. The administration of imidazole to saline-loaded animals also decreased renal TXB2 excretion but did not alter the increased excretion of renal PGE2 and 6-ketoPGF1α. This reduction in renal thromboxane biosynthesis by imidazole further increased the sodium excretion rate.

5. We suggest that TXA2 is a potent anti-natriuretic factor as well as the most potent vasoconstrictor agent known.
Effect of Bicarbonate Feeding on Intestinal Absorption of Calcium and Vitamin D Metabolism in Rats
Authors: Gafter U. , Edelstein S. , Levi J.
Published: August 2015

1. The effect of bicarbonate (NaHCO3) feeding on intestinal absorption of calcium and phosphorus and vitamin D metabolism was investigated. Gut sac uptake of 45Ca and [32P]phosphate in vitro, as well as the plasma level of vitamin D metabolites, was determined in rats fed with NaHCO3 for 9 days and their pair-fed controls.

2. Duodenal uptake of 45Ca and [32P]phosphate by alkalotic rats was less than duodenal uptake by controls. 1,25(OH)2D plasma level was much higher in alkalotic rats than in their controls, and 25(OH)D slightly higher than in controls.

3. These data suggest that NaHCO3 feeding causes a substantial increase in 1,25(OH)2D plasma level, but interferes with calcium and phosphorus absorption in the duodenum.
Liver-Specific Autoantibodies in Chronic Hepatitis B Virus Infection
Authors: Meliconi R. , Facchini A. , Miglio F. , Trevisan A. , Alberti A. , Realdi G. , Baraldini M. , Gasbarrini G.
Published: August 2015

1. Anti-liver-specific protein (LSP) antibody and liver membrane autoantibody (LMA) have been evaluated in 88 patients with hepatitis B virus (HBV)-induced chronic liver disease by means of radioimmunoprecipitation and immunofluorescence. Among our patients, 38 presented circulating HBe antigen while 43 had HBe antibody and seven were negative for both.

2. Anti-LSP was mainly found in HBeAg positive chronic active hepatitis (CAH), anti-HBe in positive CAH and in anti-HBe positive chronic persistent hepatitis (CPH).

3. Similar prevalences of LMA (range 13-33%) were detected in the various groups studied.

4. Taking into account the histological diagnosis of disease activity (periportal inflammation and piecemeal necrosis) no significant differences were found between active and inactive patients.

5. Taking into account the HBeAg/anti-HBe status, no significant differences were found between the patients positive for ‘e’ antigen or ‘e’ antibody.

6. Humoral autoimmune reactions may also play a role in HBV-induced chronic (active) liver disease irrespective of HBeAg/anti-HBe status and hence of the viral replication activity of the patients.
Vitamin D Metabolism in Patients Intoxicated with Ergocalciferol
Authors: Mawer E. Barbara , Hann J. T. , Berry Jacqueline L. , Davies M.
Published: August 2015

1. Vitamin D metabolites were measured on admission in eight patients intoxicated with ergocalciferol (serum calcium 3.01-4.05 mmol/l) and also during the subsequent 2 months in six of the eight.

2. Serum concentrations of 25-hydroxyergocalciferol, on admission, were grossly elevated in all patients (range 583-1843 nmol/l).

3. Serum calcium concentration was related significantly only to the concentration of 25-hydroxyergocalciferol (P = 0.003).

4. Concentrations of 25-hydroxyergocalciferol in serum were significantly related to those of calciferol (P = 0.004).

5. Elevated initial concentrations of 1,25-dihydroxycalciferol, mainly as 1,25-dihydroxyergocalciferol, were found in seven of the eight patients (range 179-313 pmol/l).

6. It is suggested that the hypercalcaemia in these patients may be explained by the action of 25-hydroxyergocalciferol at high concentration in competing for 1,25-dihydroxycalciferol receptors, thus exerting a biological effect per se, and also by increasing the synthesis of 1,25-dihydroxycalciferol through a mass-action effect on the renal 1α-hydroxylase.
Abnormal Regulation of Venous Alanine after Glucose Ingestion in Myotonic Dystrophy
Authors: Moxley Richard T. , Kingston William , Griggs Robert C.
Published: August 2015

1. The concentration of amino acids in whole blood was measured before and during standard 5 h oral glucose tolerance testing in six male patients with myotonic dystrophy and five normal males. The plasma levels of insulin and glucose were also determined.

2. From 90 to 240 min after glucose ingestion there was a striking decline in venous alanine concentration in the patients with myotonic dystrophy in contrast to a slight rise in alanine in the normal group.

3. The patients displayed normal glucose tolerance, and there was a sustained fall in the venous concentration of the insulin-sensitive amino acids comparable with that seen in the normal controls. However, the patients showed a threefold increase of plasma insulin after glucose.

4. These data indicate an abnormal regulation of alanine in myotonic dystrophy which may be the result of an alteration in muscle synthesis of this amino acid. This defect in alanine synthesis may be due to a decreased availability of intracellular pyruvate caused by the insulin resistance that exists in these patients.
The Contribution of Endogenous urea to Faecal Ammonia in man, Determined by 15N Labelling of Plasma Urea
Authors: Wrong O. M. , Vince A. J. , Waterlow J. C.
Published: August 2015

1. To establish the role of endogenous urea as a source of faecal ammonia, the plasma urea of two healthy men was labelled with 15N at a constant level for several days and its 15N enrichment was compared with that of faecal ammonia and total nitrogen.

2. Faeces collected after one complete gastrointestinal transit from the onset of plasma labelling had ammonia 15N enrichments which were only 8.5 ± 1.2% and total nitrogen enrichments which were 6.8 ± 0.7% of the plasma urea 15N enrichment.

3. These results show that endogenous urea is not the main precursor of faecal ammonia, which is probably derived by bacterial deamination from the protein of dietary residues, intestinal secretions and shed epithelial cells. The minor contribution of endogenous urea to faecal ammonia suggests that the lumen of the large bowel is not the main site of endogenous urea hydrolysis. The similar labelling of faecal total nitrogen and ammonia nitrogen supports other evidence that these faecal nitrogen fractions are in a constant state of exchange.
Amyloid ‘degrading factor activity': a non-specific calcium-mediated effect
Authors: Scott D. L. , Bracken P. , Bacon P. A. , Husby G.
Published: August 2015

1. The clarification of turbid AA-amyloidfibril-containing agarose gels by serum has been ascribed to degradation of the fibrils and designated as ‘amyloid degrading factor'. In the present study, sera of 32 healthy blood donors and 32 patients with rheumatoid arthritis all showed ‘degrading factor activity’ against both AA amyloid fibrils and a non-fibrillar reticulin preparation of normal liver in an agarose plate assay. AL amyloid fibrils were not affected.

2. The ‘degrading activity’ of serum was correlated with the serum albumin concentration, and the effect was also given by purified human and bovine serum albumin, although it was not seen with other serum proteins.

3. The ‘degrading activity’ of serum against AA amyloid and reticulin was significantly correlated: both substrates showed low levels in a chronic disease such as rheumatoid arthritis, and reticulin inhibited ‘degrading activity’ against AA amyloid and vice versa. These results suggest the same process involves both substrates.

4. ‘Degrading activity’ was also given by EDTA and a specific calcium chelator, and was inhibited by calcium and magnesium.

5. An enzyme inhibitor showed only partial inhibition of the ‘degrading activity’ of serum, purified albumin, and EDTA.

6. These results suggest that serum ‘degrading factor activity’ is a non-specific calcium-mediated effect against AA amyloid and reticulin preparations dispersed in agarose. It may represent a change in the degree of aggregation of these proteins rather than being an effect of proteolytic degradation. This confirms the conclusions of other workers that amyloid ‘degrading factor activity’ is an phenomenon in vitro of doubtful pathophysiological significance.
Total body potassium and water, and exchangeable sodium, in muscular dystrophy
Authors: Edmonds C. J. , Smith T. , Griffiths R. D. , Mackenzie J. , Edwards R. H. T.
Published: August 2015

1. Total body potassium (40K method) and total body water and exchangeable sodium (both by isotope dilution) were determined in 26 boys, aged 5-17 years, with muscular dystrophy. Total body potassium values were compared with measurements in a large series of normal boys on the basis of height.

2. Total body potassium was reduced even in the youngest patients and was only slightly higher in the older boys, despite their considerably greater height. Exchangeable sodium increased with increasing height in a way similar to that of normal boys. Total body water was also reduced but increased with growth, although to a lesser extent than expected for normal boys. The total body water measurements indicated that many of the affected boys were very obese, despite an apparently normal body weight.

3. An intravenous bolus of 22Na distributed at a similar rate in boys with muscular dystrophy to that in normal males.

4. In relation to the predicted values, total body potassium and 24 h urinary creatinine excretion of the affected boys both declined at a rate of 4% per year.
Interaction of renal prostaglandins with the renin-angiotensin and renal adrenergic nervous systems in healthy subjects during dietary changes in sodium intake
Authors: Kramer Herbert J. , Stinnesbeck Bruno , Klautke Georg , Kipnowski Jochen , Klingmueller Dietrich , Glaenzer Kilian , Duesing Rainer
Published: August 2015

1. In six healthy subjects the role of renal prostaglandins (PG) in modulating the actions of the renin-angiotensin and renal adrenergic nervous systems on renal function was investigated.

2. During high dietary sodium intake (350 mmol/day) for 4 days no changes in urinary excretion of PGE2, PGF2α, noradrenaline or adrenaline were noted, whereas plasma renin activity (PRA) and urinary aldosterone excretion were suppressed.

3. After 4 days of low sodium intake (35 mmol/day) urinary excretion of PGE2, aldosterone and noradrenaline, as well as PRA, had significantly increased.

4. Inhibition of PG synthesis with indomethacin (2 mg/kg body weight) had no effects on renal function on day 5 of high sodium intake. Despite suppression of PRA and urinary aldosterone, indomethacin significantly reduced p-aminohippurate (PAH) clearance, glomerular filtration rate (GFR) and urinary sodium excretion on day 5 of low sodium intake, when urinary noradrenaline excretion remained high.

5. The results point to the crucial role of the renal adrenergic nervous system in controlling renal vascular resistance and sodium conservation in healthy subjects during low sodium intake, which is unmasked when renal PG synthesis is blocked by indomethacin. Enhanced renal PG synthesis during sodium restriction therefore not only attenuates the vascular and tubular effects of the renin-angiotensin system but, more importantly, also those of the highly stimulated renal adrenergic nervous system.
AUTHOR'S REPLY
Authors: Anderson W. P. , Korner P. I.
Published: August 2015

Huisman and de Zeeuw consider that the acute haemodynamic events which follow renal artery stenosis may be due to spasm and subsequent relaxation of the renal artery, and disagree with our explanations [l, 21. In addition, they suggest that baroreceptor reflexes are responsible for the absence of a rise in arterial pressure after complete occlusion of the renal artery and reject our simple hydraulic explanation. We believe that these alternative explanations, though plausible, are incorrect.
Platelet fatty acid composition in relation to fatty acid composition in plasma and to serum lipoprotein lipids in healthy subjects with special reference to the linoleic acid pathway
Authors: Boberg M. , Croon L. B. , Gustafsson I.-B. , Vessby B.
Published: August 2015

1. The fatty acid composition in platelet phospholipids and in the plasma lipid esters as well as the serum lipoprotein lipid concentrations were determined in 67 healthy male subjects in order to establish the relationships between blood lipids and platelets.

2. A positive correlation was found between the concentrations of the triglyceride rich serum lipoprotein lipids and the relative percentage of saturated and monounsaturated fatty acids in plasma. The correlations were also positive between the serum high density lipoprotein-cholesterol concentration and the relative content of linoleic acid in the plasma cholesterol esters and phospholipids.

3. Negative correlations were found between the relative percentage of saturated and monounsaturated fatty acids in the plasma lipid esters versus linoleic acid in plasma and in the platelets. On the other hand there were positive correlations between linoleic acid in the plasma lipid esters and in the platelet phospholipids. These results indicate a direct dietary influence on the platelet phospholipid fatty acid composition.

4. The correlations between the fatty acids of the n −6 series within plasma and platelets as well as between plasma and platelets indicate that a high linoleic acid content is not associated with an increased arachidonic acid concentration. The results also indicate that the limiting metabolic step in the conversion of linoleic acid into arachidonic acid may be located at different levels in plasma and in the platelets.
Lack of effect of indomethacin on systemic and splanchnic haemodynamics in portal hypertensive rats
Authors: Blanchart A. , Hernando N. , Fernández-Muñoz D. , Hernando L. , López-Novoa J. M.
Published: August 2015

1. Portal hypertension was produced experimentally in rats by partial constriction of the portal vein.

2. Twelve rats were injected daily with indomethacin, 4 mg/kg body weight, and 12 with the vehicle (80% ethanol, 0.5 ml/day).

3. There were no differences in portal-systemic shunts nor systemic or splanchnic haemodynamics between indomethacin-treated and untreated rats.

4. These results suggest that cyclo-oxygenase products do not play a significative role in haemodynamic alterations shown by portal-ligated rats.
Catecholamines and the control of metabolism in man
Authors: Macdonald I. A. , Bennett T. , Fellows I. W.
Published: August 2015

Introduction: The physiological effects of catecholamines can result from a combination of increased activity of the sympathetic nervous system and secretion from the adrenal medulla. However, studies in the rat have revealed circumstances in which adrenal medullary secretion can occur at a time when the activity of the sympathetic nervous system is suppressed [1]; furthermore, in the lamb there may be variations in the relative amounts of noradrenaline and adrenaline secreted from the adrenal medulla [2]. It is not known whether such phenomena occur in man.
Exercise blood pressure and baroreflex function in borderline hypertensive and normotensive young men
Authors: Welsh Kevin , Ward Ann , Hanson Peter
Published: August 2015

1. Resting carotid baroreflex sensitivity and blood pressure responses to standardized conditions of rest and exercise were measured in 17 borderline hypertensive males and 12 normotensive males.

2. The borderline hypertensive group had significantly higher systolic and diastolic blood pressures during orthostatic rest and isometric handgrip exercise and higher systolic blood pressure during supine rest and submaximum and maximum treadmill exercise.

3. The borderline hypertensive group had an attenuation of baroreflex sensitivity compared with the normotensive group. Resting baroreflex sensitivity was significantly correlated with absolute systolic blood pressure during supine rest, orthostatic rest, isometric handgrip exercise and submaximum treadmill exercise.

4. The results indicate that blood pressure is regulated at a significantly higher level during rest and exercise in borderline hypertension and is associated with reduced baroreflex sensitivity measured at supine rest.
Direct measurement of vascular α1-adrenoceptors
Authors: Hoffman Brian B. , Tsujimoto Gozoh
Published: August 2015

1. α-Adrenoceptors play an important role in regulating vascular tone. [125I]BE2254, a high affinity antagonist, has been utilized to label α1-receptors in membrane preparations from rabbit aorta. [125I]BE2254 specifically labels a single class of binding sites with the characteristics of α1-receptors.

2. Catecholamines compete for [125I]BE2254 binding stereospecifically and with the characteristic α-adrenergic potency series (−)-adrenaline ≥ (−)-noradrenaline ≪ (−)-isoprenaline.

3. The α1-adrenoceptor selective antagonist prazosin is much more potent than yohimbine in competing for the [125I]BE2254 binding sites, which suggests that the α-adrenoceptor identified is predominantly of the α1 subtype.

4. The extension of radioligand binding techniques to individual rabbit aortas should simplify the study of vascular α-adrenoceptor regulation.
Role of α-adrenoceptors in vascular control
Authors: Bevan John A. , Bevan Rosemary D. , Laher Ismail
Published: August 2015

In an animal at rest, the major mechanism determining the peripheral resistance is myogenic or basal tone [1]. This is the tone that arises in vascular smooth muscle cells as a result of their stretch by the intravascular pressure: the arterial pressure and its excursions. This stretch of the wall is related, albeit indirectly, to the function of the heart. At rest the influence of the sympathetic nervous system and the adrenal gland on the vasculature via the α-adrenoceptor, although present, is not dominant. However, during activity, and particularly during stress of various kinds such as exercise, emotions, changes in altitude and temperature etc., other factors, one of which is the α-adrenoceptor-mediated influence, become relatively more important and form a major pathway of homoeostatic adaptation. It must be borne in mind that the α-adrenoceptor mechanism is only one of a number of possible influences on the vasculature, which include β-adrenoceptor activation, non-catecholamines, peptide, purine and other putative or modulator transmitter systems, and also circulating substances such as vasopressin, angiotensin and other peptides.
α-Adrenoceptor regulation in vivo and in vitro in the rabbit
Authors: Hamilton C. A. , Jones C. R. , Reid J. L.
Published: August 2015

1. The relationship between α-adrenoceptor number and response has been studied in rabbits under a range of physiological and pathological conditions.

2. The effects of irreversible α-adrenoceptor blockade, maturation, ageing, oestrogen treatment, adrenaline infusion, perinephritis hypertension and sinoaortic denervation on α-adrenoceptor number and response were examined.

3. α-Adrenoceptor number was measured by radioligand binding. [3H]Prazosin and [3H]clonidine were used as ligands to measure α1- and α2-adrenoceptor number in spleen and [3H]yohimbine to measure α2-adrenoceptor number on platelets. Responses in vivo were studied by examining the pressor responses to a range of α-adrenoceptor agonists. The functional response of platelets was examined in vitro by using the aggregatory response to adrenaline.

4. Reductions in α2-adrenoceptor ligand binding were consistently accompanied by equivalent reductions in α2-adrenoceptor-mediated responses. In contrast large reductions in [3H]prazosin binding were observed with little or no change in α1-adrenoceptor-mediated responses.

5. These results would be consistent with a large receptor reserve for α1-adrenoceptors but few if any spare α2-adrenoceptors in the vasculature or on platelets.

6. Increased responses to both α1- and α2-adrenoceptor agonists were observed in animals with sinoaortic denervation and to α1-adrenoceptor agonists in rabbits with perinephritis hypertension. These increases in response were not accompanied by increases in radioligand binding and may be related to alterations in the coupling of receptor activation to end-organ response.
Vascular α-adrenoceptors in man: interactions with adrenaline and noradrenaline
Authors: Brummelen Peter Van , Jie Kenneth , Vermey Pieter , Timmermans Pieter B. M. W. M. , Zwieten Pieter A. Van
Published: August 2015

1. Adrenaline and noradrenaline were infused in cumulative doses into the brachial artery of six healthy volunteers and changes in forearm blood flow (FBF) were measured by plethysmography. The catecholamines were infused together with saline, yohimbine and doxazosin, in that order. All infusions were given in the presence of intraarterial propranolol - to prevent β-adrenoceptor-mediated effects.

2. Adrenaline and noradrenaline reduced FBF significantly. This decrease in FBF was significantly attenuated by doxazosin as well as by yohimbine. No differences were found between adrenaline and noradrenaline.

3. It is concluded that postjunctional α1- and α2-adrenoceptors are involved in the vasoconstriction caused by exogenous adrenaline and noradrenaline in man. The relevance of circulating adrenaline for the α2-adrenpceptor-mediated contribution to basal vascular tone remains to be established.
Bile Lipid Secretion in Obese and Non-Obese Individuals with and without Gallstones
Authors: Reuben A. , Maton P. N. , Murphy G. M. , Dowling R. H.
Published: August 2015

1. Biliary lipid secretion rates were measured in non-obese and obese individuals with and without cholesterol gallstones, using a steady-state, amino acid duodenal perfusion method. In addition, biliary lipid secretion rates were measured in five obese gallstone patients receiving high-dose chenodeoxycholic acid therapy (16-22 mg day−1 kg−1).

2. Bile acid secretion rates in the non-obese patients with cholesterol gallstones (563+sem 70 μmol/h, n = 6) were significantly lower than in the non-obese controls (1078 + 210 μmol/h, n = 10, P < 0.05), whereas cholesterol secretion rates were similar in the non-obese individuals with and without gallstones (51+7 and 42+4 μmol/h respectively).

3. In the obese, both with and without gallstones, the major abnormality was hypersecretion of cholesterol (107+7 μmol/h, n = 7, and 81 + 15 μmol/h, n = 7, respectively). Both these values were significantly greater than those in the non-obese controls (P < 0.01-0.02).

4. Biliary cholesterol secretion rates correlated significantly with bile acid secretion rates but, for every mole of bile acid secreted, the obese secreted more cholesterol than the non-obese.

5. Chenodeoxycholic acid treatment lowered biliary cholesterol saturation in obese gallstone patients by reducing biliary cholesterol secretion.

6. These results suggest that there are two major types of defect in biliary lipid secretion in gallstone patients: reduced biliary bile acid secretion in non-obese gallstone patients and excessive biliary cholesterol secretion in the obese.
Thyroid Stimulating Immunoglobulins: Measurement and Clinical use
Authors: Ollis C. A. , Tomlinson S. , Munro D. S.
Published: August 2015

Graves’ disease is the commonest form of hyperthyroidism in which excessive production of thyroid hormones by the hyperplastic overactive thyroid gland produces elevated serum levels of the thyroid hormones tri-iodothyronine (T3) and thyroxine (T4). Many of the manifestations of Graves’ disease, increased basal metabolic rate, increased heart rate, heat intolerance, sweating and nervousness, can be attributed to the peripheral actions of the excess thyroid hormones. The pathogenesis of many of the other dramatic features of Graves’ disease, such as the eye involvement or localized skin changes, is not fully understood, but circulating immunoglobulins with thyroid stimulating activity are almost certainly linked to excess thyroid hormone production and thereby cause the hyperthyroidism.
Evaluation of a Non-Invasive Method for the Measurement of Metabolic rate in Humans
Authors: Weissman Charles , Damask Michael C. , Askanazi Jeffrey , Rosenbaum Stanley H. , Kinney John M.
Published: August 2015

1. Measurements of oxygen consumption (VO2) and carbon dioxide production (VCO2) can be used to calculate energy expenditure. Such data are useful in the nutritional management of a variety of pathological conditions.

2. This study is an evaluation in vitro and in vivo of the mating of a canopy and a Beckman metabolic measurement cart 1 (MMC). The canopy allows for the collection of expired gases without facial attachments.

3. Studies in vitro demonstrated the necessity of calibrating the CO2 analyser at the concentrations used in such a system (0.50-0.80% CO2). Measurements of Vo2 were within +12% to −8% of predicted values, and when calibrated at 0.50% and 0.75% CO2, measurements of Vco2 were within +2% and −7% of predicted values.

4. The studies in vivo revealed that VO2 and Vco2 were within ± 11% of the values obtained by using a canopy-spirometer-computer system.

5. The MMC plus canopy may provide an alternative method for the clinical measurement of Vo2 and Vco2, especially in subjects unable to tolerate a tight-fitting mask for prolonged periods.