bluuebunny/crossref_metadata_2025 huggingface dataset:
The Distribution and Storage of Vitamin D and its Metabolites in Human Tissues
Authors: Mawer E. Barbara , Backhouse Joan , Holman Carlene A. , Lumb G. A. , Stanbury S. W.
Published: August 2015

1. The distribution of vitamin D and its metabolites in human tissues has been studied by the combined use of radioactive cholecalciferol and biological assays of antiricketic activity in tissue extracts.

2. Injected radioactive cholecalciferol was cleared rapidly from the blood; unchanged vitamin D and various metabolites were detected subsequently in all tissues examined. The highest concentration of biological activity and radioactivity was in fat; this and, to a lesser extent, other tissues were shown to retain activity over a prolonged period of time.

3. Adipose tissue and voluntary muscle are the principal sites of storage of vitamin D in man. Pre-existing tissue pools of vitamin D can, in some circumstances, invalidate the use of radioactively labelled cholecalciferol to trace the pattern of body distribution.

4. Metabolically produced 25-hydroxycholecalciferol is also taken up from the blood into many tissues, probably by protein-binding.

5. Vitamin D is excreted in bile principally as more polar metabolites. Smaller amounts of cholecalciferol and 25-hydroxycholecalciferol are also excreted, and antiricketic activity has been demonstrated in the bile of individuals treated with vitamin D.

6. An excess of cholecalciferol (or of 25-hydroxycholecalciferol) in the blood appears to be eliminated by the physicochemical processes of partition into tissue lipid and binding to tissue proteins. It is inferred tentatively that an increased concentration of vitamin D or of 25-hydroxycholecalciferol in the liver also causes an increased biliary excretion of these substances, and an increased hepatic formation and elimination of more polar metabolites of the vitamin.
Improved Atraumatic Method for Estimation of Cerebral Transit-Time in Man
Authors: Wilkinson I. M. S. , Goddard J. , Testa H. J. , Pullen B.
Published: August 2015

1. The atraumatic technique for estimating human cerebral mean transit-time (CMTT) by antecubital injection of a bolus of non-diffusible radioactive indicator has been improved.

2. The index of CMTT obtained by the new method was of correct magnitude (2·4 ± 1·1 s SD, n = 10) and underwent an appropriate and significant increase (from 2·4 ± 1·4 s SD to 4·4 ± 0·9 s SD, n = 5) in response to a 10 mmHg reduction in arterial Pco2.
Somatomedin (Sulphation Factor)-Like Activity of Homocystine
Authors: Dehnel Jennifer M. , Francis M. J. O.
Published: August 2015

1. Homocystine (10 mg/100 ml) has a significant effect on the incorporation of inorganic sulphate by rat costal cartilage in vitro.

2. The characteristic skeletal changes associated with homocystinuria due to defective cystathionine synthetase could therefore be caused by the elevated plasma concentration (1–10 mg/100 ml) of homocystine present in this disease.
Factors Influencing the Urinary Excretion of Free Catecholamines in Man
Authors: Townshend Mary M. , Smith A. J.
Published: August 2015

1. The 24 h urinary excretion of noradrenaline and adrenaline is significantly lower in recumbent than ambulant normal subjects.

2. A diurnal variation exists in catecholamine excretion, the lowest values occurring during sleep.

3. Diurnal variation in sodium excretion parallels that in noradrenaline and adrenaline loss but the cycles can be separated by acute alterations in sleep/awake pattern.

4. Diurnal variation is lost during exercise, after myocardial infarction and was absent pre-operatively in a patient with a phaeochromocytoma.

5. Acute alterations in renal blood flow, diuresis, natriuresis and urinary acidification do not alter catecholamine excretion significantly.

6. Urinary catecholamine excretion is related to physical activity and wakefulness; the normal diurnal variation is easily overriden by sustained sympatho-adrenal activity. Alterations in renal function in exercise or after myocardial infarction do not account for the observed increases in catecholamine excretion.
Metabolism of Exercising and Resting Human Skeletal Muscle, in the Post-Prandial and Fasting States
Authors: Baker Patricia G. B. , Mottram R. F.
Published: August 2015

1. Methods are described for study of metabolism of human skeletal muscle in situ, at rest and during mild sustained contraction in the fed and fasted states.

2. At rest the average oxygen uptake was 0.29 ml min−1 100 ml of muscle−1 and the carbon dioxide output was 0.22 ml. Glucose uptake was 0.49 mg min−1 100 ml of muscle−1. The respiratory quotient was 0.75, indicating that most of the glucose was being stored.

3. When subjects made hand-grips of 5% of their maximal voluntary contraction force (5% MVC) the oxygen and carbon dioxide exchanges both increased by six times while the glucose uptake increased by 70% of the resting value.

4. A 7 h fast before the observations were made severely decreased both resting and exercising glucose uptake but produced no other alteration in the metabolism of the muscle.
Determination of Leg Blood Flow During Exercise in Man: An Indicator-Dilution Technique Based on Femoral Venous Dye Infusion
Authors: Wahren J. , Jorfeldt L.
Published: August 2015

1. A dye-dilution method has been developed for the determination of leg blood flow in man. The method is based on the infusion of indicator into the distal part of the femoral vein with blood sampling from the same vein at the level of the inguinal ligament. Catheterization of the femoral artery is not required. Evidence of adequate mixing of dye and blood is presented, based on the finding of the same dye concentration in samples from two different levels in the femoral vein.

2. Leg blood flow measured by this technique at rest and during exercise in six healthy subjects was found to agree closely with simultaneous determinations with an intra-arterial indicator-dilution technique. The reproducibility of the blood-flow measurements, expressed as the coefficient of variation for a single determination, was 9·8%.

3. A routine procedure is suggested for leg blood-flow determination based on femoral venous dye infusion. Using this procedure, leg blood flow was measured in twelve healthy subjects at rest and during exercise at work loads of 100, 200, 400 and 600 kpm/min. A linear relationship was found between leg blood flow and pulmonary oxygen uptake.

4. The applicability of this method to the study of patients with occlusive arterial disease of the leg is illustrated by findings in two patients before and after vascular reconstruction.
Central and Peripheral Mechanisms in the Maintenance of Experimental Hypertension in the Rabbit
Authors: Reid John L. , Lewis Peter J. , Dollery Colin T.
Published: August 2015

1. The role of the central nervous system (CNS) in maintaining arterial pressure was investigated in two types of experimental hypertension in rabbits.

2. In rabbits with neurogenic hypertension produced by baroreceptor denervation, anaesthesia followed by injection of clonidine (1 μg/kg) into the cisterna magna lowered mean arterial pressure (MAP) from 100·5 ± 1·5 mmHg to 45·0 ± 2·5 mmHg. In normal animals treated similarly MAP fell from 79·1 ± 2·3 mmHg to 49·1 ± 3·9 mmHg.

3. In renal hypertensive rabbits with cellophane perinephritis, intracisternal clonidine decreased MAP from 117·9 ± 4·7 mmHg to 73·0 ± 4·2 mmHg.

4. Acute ganglion blockade with intravenous pentolinium (3 mg/kg) caused a maximum fall in MAP in renal hypertensive animals to 75·8 ± 5·5 mmHg. Combination of intracisternal clonidine and intravenous pentolinium did not significantly augment this fall.

5. The raised arterial pressure in neurogenic hypertension is mediated by the CNS. In renal hypertension, there is a large contribution from the CNS but there are additional non-neurogenic factors elevating the pressure.
Systemic Haemodynamics in Mild Arterial Hypertension before and after Physical Training
Authors: Sannerstedt R. , Wasir H. , Henning R. , Werkö L.
Published: August 2015

1. Five men with borderline, latent arterial hypertension of the hyperkinetic type were studied haemodynamically at rest and during dynamic exercise before and after a 6-week period of supervised physical training.

2. Tendencies to lower heart rate, cardiac output and arterial blood pressure, both at rest and during a standardized work-load, were observed after the training period, with significant differences between paired observations for the heart rate and mean arterial blood pressure during exercise. The systemic vascular resistance being unchanged, there was a certain trend to an increased widening of the arteriovenous oxygen difference, both at rest and during exercise.

3. The present findings from a small number of subjects indicate that physical conditioning of patients with latent hypertension of the hyperkinetic type contributes to a normalization of their circulation toward a normokinetic one, thereby also normalizing their blood pressure level and achieving a more economic energy expenditure in the cardiovascular system.
Antihypertensive Effect of Spironolactone in Essential, Renal and Mineralocorticoid Hypertension
Authors: Mantero F. , Armanini D. , Urbani S.
Published: August 2015

1. The hypotensive effect of spironolactone has been studied in twenty-four patients with various forms of hypertension.

2. In essential hypertension a greater fall of blood pressure was achieved in patients with renin activity hyporesponsive to postural change than in those in whom renin responded normally to posture.

3. A poor hypotensive response was observed in patients with renal or renal arterial disease and secondary aldosteronism.

4. The variable hypotensive response seen in patients with primary aldosteronism predicted the response to adrenal surgery.

5. Blood pressure was not lowered by spironolactone in one case of 17-hydroxylation deficiency or in one case of malignant ovarian arrhenoblastoma producing aldosterone.
The Possible Site of Action of Sodium Cromoglycate Assessed by Exercise Challenge
Authors: Godfrey S. , Zeidifard E. , Brown K. , Bell J. H.
Published: August 2015

1. The protective effect of different particle sizes of sodium cromoglycate (SCG) was assessed by exercise challenge in nine asthmatic patients.

2. SCG particles of 11·7 μm or 2·0 μm mass median diameter were generated by a spinning disc and compared with lactose placebo particles. The drugs were given 10 min before a 6 min run on a treadmill.

3. The post-exercise bronchoconstriction caused a 48% fall in peak flow rate in the placebo test, a 41% fall after the large SCG particles and a 20% fall after the small particles.

4. It is concluded that the site of action of SCG is probably in the smallest airways.
Investigation of Serum Lipoproteins and Apoproteins in Abetalipoproteinaemia
Authors: Kostner G. , Holasek A. , Bohlmann H. G. , Thiede H.
Published: August 2015

1. The serum lipoproteins, apoproteins and lecithin—cholesterol acyltransferase activity of three patients with abetalipoproteinaemia have been studied.

2. Concentration of lipoproteins with a density of less than 1·063 was found to be 5–6 mg/100 ml of plasma. The protein part consisted only of apoAI polypeptides.

3. Concentration of total serum high-density lipoproteins was 90–100 mg/100 ml. After total delipidization of this fraction, apoproteins were separated by column chromatography. All apoA and most of the apoC peptides could be demonstrated by immunochemical methods and polyacrylamide gel electrophoresis.

4. Quantification of individual polypeptides indicated that the proportions apoAI: apoAII: apoAIII in high-density lipoproteins were not different from those observed in normal subjects. ApoCIII1 was absent in the patients' serum. In the remaining apoC peptides differences in the distribution compared with normal subjects could be demonstrated.

5. With antibodies to lipoprotein B, acetylated lipoprotein B or apolipoprotein B no reaction could be observed with abetalipoproteinaemic serum or any density fraction tested including density 1·23 infranate.

6. Isoelectric focussing of prestained lipoproteins in complete patients' serum revealed the absence of four major lipoprotein families present in normal serum.

7. Lecithin—cholesterol acyltransferase activity of abetalipoproteinaemic serum was reduced to a value of about 50% of normal but lipoproteins of patients' serum could be utilized as a substrate only to a minor degree. The maximum activity was observed only if lipoproteins of normal serum were added to the assay system.
Detection of Mucopolysaccharidoses by Sulphate Incorporation into Stimulated Lymphocytes
Authors: Venetianer A. , Dallmann L. , László A. , Burg K.
Published: August 2015

1. A new technique has been developed for the detection of inborn errors of mucopolysaccharide metabolism by measurement of the incorporation of radioactive sulphate into lymphocytes stimulated by phytohaemagglutinin.

2. Incorporation of 35SO4 was much higher in lymphocytes of patients with mucopolysaccharidosis than in healthy subjects.

3. This technique offers a rapid, simple, reliable screening procedure for the detection of mucopolysaccharidoses.
Studies of the Peripheral Vasodilator Response to Acute Insulin-Induced Hypoglycaemia in Man
Authors: Middleton W. G. , French E. B.
Published: August 2015

1. The response of hand blood flow to acute insulin-induced hypoglycaemia was measured in normal subjects in whom vasomotor tone had been released physiologically by body heating, anatomically by unilateral nerve block and pharmacologically by unilateral intra-arterial infusion of bretylium tosylate or phenoxybenzamine. Five patients who had undergone unilateral cervical sympathectomy were also studied.

2. Under these conditions the usual increase in hand blood flow associated with acute hypoglycaemia was converted into a decrease except during complete unilateral α-adrenergic blockade when hypoglycaemia produced no change in hand blood flow.

3. The possible mechanisms responsible for the vasodilatation associated with hypoglycaemia are discussed.

4. The results suggest that release of vasoconstrictor tone, rather than activation of specific vasodilator mechanisms (neurogenic or humoral), is the principal means whereby acute hypoglycaemia produces increased blood flow in the hand.
Changes in Plasma Lipoprotein Lipids in Hypercholesterolaemic Patients Treated with the Bile Acid-Sequestering Resin, Colestipol
Authors: Clifton-Bligh P. , Miller N. E. , Nestel P. J.
Published: August 2015

1. Seven patients with type II hyperlipoproteinaemia were treated with the bile acid-sequestering resin, colestipol (5 g three times daily), after a prolonged period of taking placebo.

2. After 8–9 weeks of treatment, the plasma concentration of the non-esterified cholesterol of very-low-density lipoprotein (VLDL) had risen by a mean of 0.09 mmol/l (43% increase, P < 0.001), that of the esterified cholesterol of VLDL had risen by a mean of 0.11 mmol/l (38% increase, P < 0.01), and that of the triglyceride of VLDL had risen by a mean of 0.40 mmol/l (53% increase, P<0.001). During the same period, the plasma concentration of the non-esterified cholesterol of low-density lipoprotein (LDL) decreased by a mean of 0.44 mmol/l (26% decrease, P < 0.01), that of the esterified cholesterol of LDL decreased by a mean of 1.28 mmol/l (30% decrease, P< 0.001), and that of the triglyceride of LDL decreased by a mean of 0.04 mmol/l (8% decrease, P < 0.01). No significant changes occurred in the plasma concentration of either the cholesterol or triglyceride of high-density lipoprotein (HDL) during treatment.

3. During the early period of treatment with colestipol, changes took place in the specific radioactivity of plasma cholesterol (labelled by intravenous injection of [3H]cholesterol), which, together with the changes in the mass of cholesterol within the individual plasma lipoproteins, were consistent with an increased influx into plasma of non-esterified cholesterol within VLDL, and an increased efflux of cholesterol from plasma within LDL.
Cardiogenic Oscillations of Nitrogen and Argon Concentration in Expired Gas in Man
Authors: Bradley G. W. , Henderson A. K. , Mills R. J.
Published: August 2015

1. The cardiogenic oscillations in the concentration of nitrogen and argon in expired gas, which are seen after the inspiration from residual volume of pure oxygen or a bolus of argon, have been studied in normal subjects and in patients with atrial fibrillation.

2. In the upright position of the subject, the peaks of nitrogen and argon concentration coincide with ventricular systole, although there is a transit delay along the tracheobronchial tree before any change of concentration occurs at the mouth.

3. Studies in different postures demonstrated that the effect of the heart is predominantly due to a reduction in cardiac volume during systole with a decrease in airflow from regions adjacent to the heart. These areas contain a different concentration of nitrogen and argon in the alveolar air from the more apical regions.

4. It has been shown that the results are consistent with the present concepts of the influence of gravity on the distribution of inspired air.
The Contribution of the Kidney to the Removal of a Lactic Acid Load under Normal and Acidotic Conditions in the Conscious Rat
Authors: Yudkin J. , Cohen R. D.
Published: August 2015

1. The rate of removal from the circulation of an intravenous lactic acid load has been studied in conscious rats, previously subjected either to bilateral nephrectomy or to a sham operation.

2. In rats with normal blood pH, the apparent contribution of the kidneys to removal of the lactic acid load is 30%; less than 12% of the renal contribution is attributable to urinary excretion.

3. In bilaterally nephrectomized rats made acidotic by administration of ammonium chloride, the rate of removal of a half-neutralized lactic acid load is progressively decreased with increasing severity of acidosis. No such effect is seen in sham-operated animals.

4. An increase in the ability of the kidney to remove lactate during acidosis compensates for approximately half of the simultaneous fall in the capacity of the remainder of the body for lactate assimilation.

5. Basal blood lactate concentrations fall in the presence of metabolic acidosis.
Enzyme Activities and Properties of Lysosomes and Brush Borders in Jejunal Biopsies from Control Subjects and Patients with Coeliac Disease
Authors: Peters T. J. , Heath J. R. , Wansbrough-Jones M. H. , Doe W. F.
Published: August 2015

1. Reduced activities of four enzymes from brush borders were found in intestinal biopsies from patients with untreated coeliac disease. The activities returned towards control values after treatment by gluten withdrawal. Parallel changes were noted for the cytosol enzyme lactate dehydrogenase.

2. Measurement of brush-border integrity by differential centrifugation of biopsy extracts indicated increased fragility of the brush borders in biopsies from untreated patients. Normal values were obtained for biopsies from treated patients.

3. Increased activities of six acid hydrolases (lysosomal enzymes) were found in biopsies from untreated coeliac patients. Normal values were obtained for biopsies from treated patients.

4. Assessment of lysosomal integrity by assay of latent N-acetyl-β-glucosaminidase and of sedimentable activity of four acid hydrolases demonstrated increased lysosomal fragility in untreated coeliac mucosa. These lysosomal changes return to within the normal range after treatment by gluten withdrawal.

5. The lysosomal changes are consistent with their having a pathogenic role in the enterocyte damage of coeliac disease. Possible mechanisms for the lysosomal changes are discussed.
The Central Hypotensive Action of Clonidine and BAY 1470 in Cats and Rats
Authors: Finch L.
Published: August 2015

1. Intraventricular clonidine and BAY 1470, administered in small doses to conscious renal hypertensive cats, produced a fall in mean blood pressure lasting for a period of 3 h. This fall in blood pressure was accompanied by a marked bradycardia.

2. Pretreatment with intraventricular phentolamine (0.3–6 μmol), piperoxan (0.18–0.74 μmol) or tolazoline (0.35–1 μmol) abolished the hypotensive effects of intraventricular clonidine (74 nmol), whereas pretreatment with haloperidol (2.6 μmol/kg, intraperitoneally), or desmethylimipramine (3.3 μmol/kg, intraperitoneally, or 1.7 μmol, intraventricularly) did not modify the cardiovascular responses to clonidine.

3. Emesis was observed 1 min after intraventricular administration of clonidine (18–112 nmol) or BAY 1470 (0.07–0.14 μmol), which always preceded the cardiovascular actions and was still observed after pretreatment with haloperidol, desmethylimipramine, phentolamine, piperoxan or tolazoline.

4. In conscious hypertensive rats clonidine (0.6 μmol/kg, intraperitoneally) produced a marked fall in blood pressure that was antagonized by centrally acting α-adrenoreceptor blocking agents but not modified by pretreatment with either 6-hydroxydopamine (three doses of 1 μmol, intraventricularly) or 5,6-dihydroxytryptamine (0.1 μmol).

5. It is concluded that the anti-hypertensive responses to clonidine are mediated via stimulation of central α-adrenoreceptors and are independent of central dopaminergic receptors, intact central serotonergic neurons and intact adrenergic uptake mechanisms.
Paradoxical Diuresis after Vasopressin Administration to Patients with Neurohypophyseal Diabetes Insipidus Treated with Chlorpropamide, Carbamazepine or Clofibrate
Authors: Meinders A. E. , Van Leeuwen A. M. , Borst J. G. G. , Cejka V.
Published: August 2015

1. Chlorpropamide, carbamazepine and clofibrate have an antidiuretic action in patients with neurohypophyseal diabetes insipidus which is qualitatively similar to that of antidiuretic hormone (ADH).

2. An additive antidiuretic effect is produced by combination of chlorpropamide and carbamazepine with small dosages of ADH.

3. After an immediate and transient antidiuresis, a single intravenous bolus injection of lysine vasopressin given during treatment with chlorpropamide, chlorpropamide with a continuous intravenous infusion of lysine vasopressin, carbamazepine or clofibrate, resulted in increased water diuresis for 12–24 h or longer.

4. This paradoxical diuresis was not observed during treatment with chlorothiazide.

5. It is suggested that the antidiuretic action of chlorpropamide, carbamazepine and clofibrate is localized at the receptor site for ADH in the distal renal tubular cell.
Plasma Catecholamines and Renin Activity in Response to Exercise in Patients with Essential Hypertension
Authors: Chodakowska J. , Nazar K. , Wocial B. , Jarecki M. , Skórka B.
Published: August 2015

1. The effect of physical exercise on blood pressure, plasma catecholamines and plasma renin activity was studied in fourteen patients with essential hypertension and in eight healthy subjects.

2. Resting plasma noradrenaline and adrenaline and plasma renin activity of the hypertensive patients did not differ from those of the control subjects.

3. In response to graded exercise producing successive heart rates of 120, 140 and 160 beats/min, significantly greater increases of blood pressure were found in the patients than in the control subjects.

4. Plasma noradrenaline increased significantly in both groups at all levels of exercise, the responses being significantly greater in the hypertensive patients.

5. The mean arterial blood pressure was significantly correlated with plasma noradrenaline concentration in the control subjects but not in the hypertensive patients.

6. In the hypertensive group plasma adrenaline increased significantly after exercise at all work loads whereas, in the control group, significant increase occurred only at the highest work load. The differences in the response of the two groups were significant at each work load.

7. Plasma renin activity increased significantly after exercise at the heart rate of 120 beats/min, both in the hypertensive patients and in the control subjects. The magnitude of the response was similar in the two groups.
Lipoprotein Lipase and Hormone-Sensitive Lipase Activities in Human Subcutaneous Lipomas: Comparison with Normal Subcutaneous Adipose Tissue
Authors: Giudicelli Y. , Pecquery R. , Agli B. , Jamin C. , Quevauvilliers J.
Published: August 2015

1. Lipoprotein lipase activity and hormone-sensitive lipase activity were investigated in subcutaneous lipomas removed from two patients and compared with the enzyme activities in subcutaneous adipose tissue from two normal subjects.

2. Confirmation was obtained of the presence of lipoprotein lipase activity in lipomas with an activity fifteen to forty-five times that in the two control samples.

3. Hormone-sensitive lipase activity was demonstrated in lipomas under basal conditions of assay as well as in the presence of adrenaline plus theophylline. However, compared with the non-lipomatous fat samples, these activities were lower, as was the magnitude of the lipolytic response to adrenaline plus theophylline.

4. The significance of these measurements of enzyme activity and their role in the pathogenesis of lipomas are briefly discussed.
Altered Angiotensin I Conversion in Pulmonary Disease
Authors: Oparil Suzanne , Low J. , Koerner T. J.
Published: August 2015

1. A specific method is described for the measurement of angiotensin I converting enzyme activity in plasma with 125I-labelled angiotensin I used as substrate.

2. Converting enzyme activity in plasma from fifteen normal subjects, eleven patients with sarcoidosis, twelve patients with chronic obstructive pulmonary disease and three patients with shock lung was assayed by this technique.

3. Patients with sarcoidosis had increased plasma converting enzyme activity whether or not they were receiving steroid therapy.

4. Patients with chronic obstructive pulmonary disease and shock lung had decreased plasma converting enzyme activity, but extent of conversion did not correlate with the severity of the lung disease.

5. Converting enzyme activity in normal plasma could be completely inhibited by addition of exogenous angiotensin I in 0·5–2·5 × 107 times physiological concentration. Twice as much exogenous angiotensin I was needed to inhibit conversion completely in plasma from patients with sarcoidosis; one tenth as much in chronic obstructive pulmonary disease. These results indicate that plasma has a high capacity for angiotensin I conversion even in patients with pulmonary parenchymal disease.

6. Results suggest that plasma converting enzyme activity may be a reflection of pulmonary conversion and can be altered by pulmonary disease.

7. Measurement of plasma converting enzyme activity may be useful in studies designed to characterize the regulatory role of converting enzyme in the renin—angiotensin system and in cardiovascular homeostasis.
Effects of Aldosterone and Spironolactone on Arterial Renin in Rats
Authors: Rosenthal J.
Published: August 2015

1. The metabolic role of arterial angiotensin I-forming enzyme (i.e. renin activity) was studied in total homogenates and in subcellular fractions of the aorta of normotensive and hypertensive rats.

2. Angiotensin I-forming enzyme was measured in (a) uninephrectomized rats rendered hypertensive with d-aldosterone and sodium chloride (10 g/l) drinking solution, (b) rats treated in the same manner but with the addition of spironolactone, and (c) control rats.

3. Hypertension developed in aldosterone-treated rats within 3–6 weeks and was associated with decreased plasma and renal renin values. Total aortic renin activity was up to sixfold higher in the hypertensive animals than in control animals and there was an increased ratio of supernatant to microsomal renin activity in the aorta.

4. In spironolactone-treated rats blood pressure and total aortic renin concentrations were comparable with those in the control rats.

5. The results support the hypothesis that renin generated at local vascular sites, which is independent of circulating renin levels, contributes to regulation of blood pressure.
Clinical Significance of Plasma Renin Activity in Human Renovascular Hypertension
Authors: Salvetti A. , Arzilli F. , Sassano P. , Poli L. , Pesola A.
Published: August 2015

1. Plasma renin activity (PRA) in peripheral venous blood of patients with renovascular hypertension was found to be high (thirty-five), normal (twenty-one) and low (three). Twenty-one patients with high PRA were cured or improved after successful surgery, as were eight of eleven with normal PRA and one with a low PRA. After surgery high PRA values became normal or low.

2. A β-receptor-blocking agent (oxprenolol) decreased PRA in twenty-eight patients (responders) and it either did not modify or increased PRA in the other fifteen (non-responders). All fourteen non-responders were cured by surgery, as were thirteen out of fifteen responders; ten non-responders became responders after surgery. Oxprenolol suppressed renin secretion of both kidneys of two patients with essential hypertension, and it either decreased (six) or did not modify (four) renin secretion from the ischaemic kidney.

3. PRA measurement in renal veins of twenty-six patients with renovascular hypertension showed that only the ischaemic kidney contributes to the peripheral PRA, renin secretion being suppressed in the contralateral kidney. The suppression of renin secretion from the ischaemic kidney produced either by nephrectomy (nine) or by aortorenal by-pass (six) normalized blood pressure.

4. Peripheral PRA values are of poor diagnostic significance and PRA unresponsiveness to a β-receptor-blocking drug and the suppression of renin secretion from the ischaemic kidney are characteristic findings of renovascular hypertension curable by appropriate surgery.
Impermeability of the Blood—Cerebrospinal Fluid Barrier for Angiotensin II in Rats
Authors: Schelling P. , Hutchinson J. S. , Ganten U. , Sponer G. , Ganten D.
Published: August 2015

1. Anaesthetized, nephrectomized rats were infused intravenously with unlabelled angiotensin II (AII) or with [3H]angiotensin II (3H-labelled AII). The brain ventricular system was perfused with artificial cerebrospinal fluid. The perfusate was collected from the cisterna magna and analysed for AII by radioimmunological and biochemical methods.

2. No increase of immunoreactive AII in cerebrospinal fluid could be shown during intravenous infusion of AII.

3. During intravenous infusions of 3H-labelled AII at pressor doses small amounts of radioactivity were found in cerebrospinal fluid perfusate.

4. The radioactivity of cerebrospinal fluid outflow could not be related to AII.
The Effects of Propranolol on Spontaneous and Experimental Hypertension in the Rat
Authors: Pessina A. C. , Corgnati A. , Palatini P. , Oneglia C. , Dal Palù C.
Published: August 2015

1. The hypotensive effect of propranolol and its correlation with the changes in heart rate, plasma volume and plasma renin activity produced by this drug were studied in normotensive rats and in rats with spontaneous, renovascular and deoxycorticosterone-induced hypertension.

2. No correlation was found between the fall in arterial pressure and the reduction in heart rate and plasma volume. On the contrary, a direct correlation was found between the hypotensive response and plasma renin activity: rats with high renin showed the maximum response, those with low renin no response.

3. Studies on blood volume distribution in different organs and the direct measurement of blood flow in the splanchnic bed demonstrated a significant correlation between the effect of propranolol on capillary permeability and the haemodynamic changes which it causes, namely a significant increase in portal venous pressure.
Pharmacokinetics of β-Receptor-Blocking Agents in Relation to Their Anti-Hypertensive Effect
Authors: Gugler R. , Bodem G. , Dengler H. J.
Published: August 2015

1. β-Receptor-blocking drugs are rapidly and completely absorbed after oral administration. Systemic availability is nevertheless incomplete for propranolol, alprenolol and oxprenolol, owing to ‘first-pass’ extraction by the liver.

2. Plasma half-life is between 2 and 4 h, except for sotalol (10–12 h). Plasma elimination of propranolol is reduced with decreased liver blood flow, observed in congestive heart failure or during chronic propranolol therapy itself.

3. β-Receptor blockade is usually achieved in these concentration ranges: propranolol and alprenolol, 50–100 ng/ml; oxprenolol, 500–1000 ng/ml; pindolol, 10–30 ng/ml; sotalol, 2–6 μg/ml. Higher concentrations are often found with high doses administered to hypertensive patients.
The Effect on Blood Pressure of β-Adrenoreceptor-Blocking Drugs Given Once Daily
Authors: Wilson M. , Morgan G. , Morgan T.
Published: August 2015

1. Blood pressure was controlled to the same extent whether propranolol or pindolol was given once or three times/day.

2. The anti-hypertensive action of β-receptor-blocking drugs persisted for 36–48 h when administration ceased.
Identification and Treatment of Arterial Hypertension in General Practice
Authors: Hodes C. , Rogers P. A. , Everitt M. G.
Published: August 2015

1. A screening programme has been set up in a group general practice for identifying and treating moderate high blood pressure in men and women aged 45–54 years, and at the same time the identification and treatment of high blood pressure in patients in reference general practices has been monitored.

2. The special measures resulted in a response rate of 68·8%. In the reference practices, 14·9% of patients attending during the study had their blood pressure reading recorded on the monitoring form.

3. The overall prevalence of diastolic blood pressure (phase 4) ≥105 mmHg in the special hypertension programme is 3·8 times that observed in the reference practices.
The Relative Transfer Rates for Sodium and Xenon from Gut Lumen to Plasma in Man
Authors: Love A. H. G. , Chen L. C. , Reeve J. , Veall N.
Published: August 2015

1. A whole-gut perfusion technique has been used to compare the rates of intestinal absorption of sodium and xenon.

2. The calculated transit-time spectra for sodium and xenon across the gut mucosa do not differ significantly either in mean transit time or, for the first 15 min, in shape.

3. These results support the hypothesis that the rate of transfer of sodium from the small intestinal lumen to plasma is limited by blood flow.

4. It is suggested that some features of cholera can be explained by this hypothesis.
Human Skeletal Muscle Function: Description of Tests and Normal Values
Authors: Edwards R. H. T. , Young A. , Hosking G. P. , Jones D. A.
Published: August 2015

1. The force produced by isometric contractions of the quadriceps muscle have been studied during maximal voluntary contractions and when a substantial part of the muscle was electrically stimulated via surface electrodes.

2. In normal children and adults, the force of a maximal voluntary contraction of the quadriceps was proportional to body weight.

3. The function of the quadriceps has been described in terms of the force/frequency curve, speed of relaxation and the rate of loss of force during 18 s stimulation at 30 Hz and 100 Hz.

4. The functional characteristics of adductor pollicis when stimulated via the ulnar nerve were essentially similar to those of the quadriceps.

5. Studies of the function of these two muscles are complementary since quadriceps femoris is amenable to needle biopsy investigations of its structure and chemistry whereas adductor pollicis is more suitable for electrophysiological studies.
Plasma Renin Levels and Systemic Haemodynamics in Essential Hypertension
Authors: Fagard R. , Amery A. , Reybrouck T. , Lijnen P. , Billiet L. , Joossens J. V.
Published: August 2015

1. Plasma renin concentration, intra-arterial pressure, cardiac output and total peripheral resistance have been studied in 50 patients with essential hypertension and normal renal function.

2. Total peripheral resistance and plasma renin were negatively correlated (r = −0·45), indicating that ‘high-renin’ essential hypertension is not necessarily associated with arteriolar vasoconstriction.

3. The inverse relation between mean arterial pressure and plasma renin (r = −0·46) suggests a role for the renal baroreceptor mechanism in the suppression of renin in ‘low-renin’ hypertension.

4. Cardiac output was positively related to plasma renin concentration (r = +0·42).

5. Multiple regression analysis indicates that the described relationships were independent of age.
Renal Clearance of Unbound Bilirubin in the Rat
Authors: Elías María Mónica , Comin E. J. , Garay E. A. Rodriguez
Published: August 2015

1. Unbound or diffusible bilirubin in serum and urine was measured in rats with bile-duct ligation or after continuous infusion of unconjugated bilirubin.

2. The glomerular filtration rate was estimated by measuring the endogenous creatinine clearance and the unbound bilirubin in serum and urine was determined by a Sephadex gel filtration method.

3. Unbound bilirubin clearance was significantly lower than creatinine clearance.

4. The estimated rate of bilirubin reabsorption (calculated from the difference between the unbound bilirubin filtered load and the bilirubin excreted in the urine) was directly related to the serum unbound bilirubin concentration and the unbound bilirubin filtered load.

5. The results suggest that the main mechanism of urinary excretion of bilirubin in the rat involves glomerular filtration and tubular reabsorption by diffusion.
The Passage of Apoproteins from Plasma Lipoproteins into the Lipoproteins of Peripheral Lymph in Man
Authors: Reichl D. , Myant N. B. , Pflug J. J. , Rudra D. N.
Published: August 2015

1. The transport of apoprotein B from the lipoproteins of plasma into the lipoproteins of lymph draining the foot has been studied in four men with type III hyperlipoproteinaemia.

2. Three subjects were given autologous 125I-labelled very-low-density lipoprotein (VLDL) and 131I-labelled low-density lipoprotein (LDL) by intravenous injection; the fourth was given autologous 125I-labelled VLDL and 131I-labelled intermediate-density lipoprotein (IDL) plus LDL.

3. The 125I/131I ratios in serum and lymph apoprotein B, and the 125I and 131I specific radioactivities of apoprotein B in VLDL, IDL and LDL from serum and lymph, indicate that apoprotein B in the circulating VLDL can reach peripheral lymph without the intermediacy of circulating LDL.
Some Aspects of Sodium Movement across Porcine Aortic Walls in Vitro
Authors: Edwards I. R.
Published: August 2015

1. Sodium movement across the porcine aortic arch in vitro is greater from the intimal to the medial surface than in the reverse direction.

2. A short-circuit current can be measured across the aortic arch and the calculated energy is greater than the energy required to support the net outward sodium movement, suggesting the possibility of active transport of other ions.

3. Net sodium movement is not significantly altered by an adverse gradient on the outside (medial side) but is reduced by a gradient in the opposite direction.

4. Sodium retention within the tissue is increased by a gradient on the medial side.

5. The movement of [14C]inulin is greater from the medial to the intimal surface, suggesting greater porosity on the medial side. A slight rise in both total tissue fluid and extracellular fluid occurred when the sodium concentration on the medial side of the preparation was increased. This did not occur with the sodium concentration increased on the intimal side. The changes were only significant statistically for total tissue fluid.

6. The short-circuit current can be enhanced by adrenaline and reduced by a variety of β-adrenoreceptor-blocking agents.

7. It appears that aortic tissue can actively transport sodium and it is suggested that this mechanism could play a part in blood pressure control.
Reflex Control of Renin Release in Essential Hypertension
Authors: Mancia G. , Leonetti G. , Terzoli Laura , Zanchetti A.
Published: August 2015

1. The reflex control of renin release was studied in subjects with essential hypertension by comparing the effects of a variable-pressure neck chamber and head-up tilting.

2. Increase in carotid sinus transmural pressure (obtained by reducing tissue pressure outside the carotid sinus by 34 ± 3 mmHg) decreased mean arterial pressure by 16 ± 2 mmHg, but did not reduce significantly the renal venous—arterial difference in plasma renin activity. Likewise decrease in carotid sinus transmural pressure (obtained by increasing tissue pressure outside the carotid sinus by 39 ± 2 mmHg) increased mean arterial pressure by 14 ± 3 mmHg, but caused only a very slight increase in the renal venous—arterial difference in plasma renin activity.

3. Passive tilting reduced mean arterial pressure by 9 ± 1 mmHg. In this circumstance the renal venous—arterial difference in plasma renin activity increased significantly and markedly.

4. It is concluded that in essential hypertension the carotid sinus baroreceptors, though active in blood pressure control, do not exert a major influence on renin release. In these patients reflex increase of renin during tilting is apparently mediated through other receptors than those in the carotid sinuses.
Lack of a Role for the Renal Nerves in Renal Sodium Reabsorption in Conscious Dogs
Authors: Lifschitz M. D.
Published: August 2015

1. Studies in anaesthetized animals suggest that the renal nerves have a role in the regulation of sodium excretion. Urinary sodium excretion decreases when the renal nerves are stimulated and increases after renal denervation or ganglionic blockade. In order to define the role of the renal nerves in the regulation of urinary sodium excretion in awake animals, dogs were prepared with one kidney denervated and the other intact and the bladder split so that urine could be collected from each kidney. Denervation was confirmed by kidney noradrenaline analysis (1·72 ± 0·29 vs 0·18 ± 0·12 nmol/g).

2. These dogs were studied awake with one of two protocols on each of two separate days. In protocol VH, volume expansion (5% body weight) was followed by haemorrhage of 2% body weight. Fractional sodium excretion fell from 4·7 ± 0·5 to 1·1 ± 0·2% on the denervated side and from 5·6 ± 0·6 to 1·4 ± 0·3% on the intact side. Inulin and p-aminohippurate clearance fell similarly on both sides.

3. In protocol HV, haemorrhage of 2% body weight was followed by blood replacement and volume expansion of 5% body weight. In this second protocol fractional sodium excretion during haemorrhage was 0·23 ± 0·07 and 0·24 ± 0·09% for denervated and intact kidneys respectively and increased to 2·04 ± 0·32 and 2·78 ± 0·60 after volume expansion.

4. In both protocols the denervated kidney was able to reabsorb sodium as well as the innervated kidney during haemorrhage and was able to increase fractional sodium excretion as well as the denervated kidney during volume expansion. These results suggest that the renal nerves do not have a significant role in the regulation of sodium excretion in conscious animals.
Effects of Airway Anaesthesia on the Ability to Detect Added Inspiratory Resistive Loads
Authors: Chaudhary B. A. , Burki N. K.
Published: August 2015

1. The effects of airway anaesthesia on the ability to detect added inspiratory resistive loads were studied in normal subjects. A 4% solution of lignocaine hydrochloride was used for anaesthesia of the airways.

2. After anaesthesia of the mouth and upper always to the level of the vocal cords there was a significant deterioration in the detection ability expressed in terms of the absolute added resistance (ΔR), with a concomitant increase in pulmonary resistance (Rint.). However, there was no significant change in the detection ability expressed in terms of the ratio of ΔR to the sum of Rint. and the minimal resistance of the apparatus (ΔR/R0).

3. After combined anaesthesia of the upper and lower airways there was no significant change in pulmonary resistance or in the detection ability expressed either as ΔR or as ΔR/R0.

4. We conclude that, in normal subjects, the main site of detection of added inspiratory resistive loads does not lie in the upper or lower airways. Our results and those of previous studies suggest that the diaphragm is the most likely site of detection of added resistive loads.
Induction of Lysinuria in the Rat by Two Para-Substituted Guanidinophenylalanines
Authors: Owens C. W. I.
Published: August 2015

1. p-Guanidino- and p-guanidinomethyl-phenylalanine increase the renal excretion of lysine especially and, to some extent, cystine in the phenylalanine-loaded rat. The methyl derivative is the more effective.

2. The lysinuria is dose-dependent, reversible, pronounced when the intravenous infusion of analogue exceeds 10 μmol min−1 kg−1 and does not appear to be secondary to changes in urine flow or sodium excretion.

3. A mechanism for induced basic aminoaciduria conditions is suggested.
Intestinal Absorption and Tissue Retention of Cadmium and Calcium in Normal Adult Rats and Rats Given an Active Metabolite of Vitamin D (1,25-Dihydroxycholecalciferol)
Authors: Lorentzon R. , Larsson S.-E.
Published: August 2015

1. Nine-months-old male rats were divided into a normal control group and one experimental group which received eight daily intraperitoneal injections of 15 pmol of 1,25-dihydroxycholecalciferol/100 g body weight. After 5 days, 20 μCi of 109CdCl2 or 20 μCi of 45CaCl2 was administered by stomach tube. The intestinal absorption and tissue retention of the radioisotopes were analysed during the next 3 days, the animals being kept in metabolic cages.

2. The administration of 1,25-dihydroxycholecalciferol caused significantly increased net absorption of intestinal calcium, hypercalcaemia and increased incorporation of calcium into bone. In comparison, there was no significant effect on the intestinal absorption of trace doses of cadmium or upon the accumulation of cadmium in the liver and kidneys.
Validation of ‘Transit Renography’ for the Determination of the Intrarenal Distribution of Plasma Flow: Comparison with the Microsphere Method in the Anaesthetized Rabbit and Pig
Authors: Wilkinson S. P. , Bernardi M. , Pearce P. C. , Britton K. E. , Brown N. J. G. , Poston L. , Clarke M. , Jenner R. , Williams Roger
Published: August 2015

1. The spectrum of transit times of sodium o-iodohippurate (Hippuran) through the kidney can be derived from an 131I- (or 123I-) labelled Hippuran renogram by deconvolution. In the rabbit and pig, as has previously been shown in man, the frequency distribution curve for the transit times was bimodal. Since the transit time is likely to be proportional to the nephron length, the area of the first mode is likely to represent plasma flow to the shorter outer cortical nephrons whereas the delayed mode represents flow to the long juxtamedullary nephrons.

2. This interpretation was tested by simultaneously comparing renography with the microsphere method of measuring intrarenal plasma flow distribution in 12 rabbits and two pigs with a variety of anaesthetics. A close agreement was found between both methods for the percentage of plasma flow distributed to the outer cortical nephrons, thus supporting the use of ‘transit renography’ to determine the intrarenal distribution of plasma flow.
A Survey of Salivary Kallikrein and Amylase in a Population of Schoolgirls, throughout the Menstrual Cycle
Authors: Bhoola K. D. , Matthews R. W. , Roberts Fiona
Published: August 2015

1. The values for kallikrein, amylase and protein were determined in samples of saliva obtained from 220 girls aged 14–18 years.

2. The concentrations of protein and amylase and kallikrein activities (per ml of saliva) were considerably more variable in samples taken in the morning than those in the afternoon.

3. The median amylase activity was about two and a half times greater in the morning than that in the afternoon. No such differences were seen in the median values for protein or kallikrein.

4. Examination of the values for salivary kallikrein during the menstrual cycle showed that there was significantly greater activity during days 29–32 and 1–4 than during the rest of the cycle. This pattern was most marked in the morning values of kallikrein but not apparent either in the morning or in the afternoon values of protein or amylase.