bluuebunny/crossref_metadata_2025 huggingface dataset:
Role of the Autonomic Nervous System in Mild Human Hypertension
Authors: Julius S. , Esler M. D. , Randall O. S.
Published: August 2015

1. Some of the haemodynamic abnormalities in mild (borderline) human hypertension appear to be neurogenic, since they can be completely abolished by pharmacological autonomic blockade.

2. The cardiac output is elevated in 30% of patients through increased sympathetic drive and decreased parasympathetic inhibition.

3. In the remainder, the higher blood pressure is maintained by increased total peripheral vascular resistance.

4. In approximately 30% of this latter group, the higher vascular resistance is maintained solely by increased alpha-adrenergic tone.

5. Elevated plasma renin activities in a proportion of cases are probably due to generalized increase in sympathetic nervous activity.

6. Patients with mild hypertension thus show increased sympathetic drive to the heart and arterioles as well as decreased cardiac parasympathetic inhibition. It is presumed that the increased plasma renin is also neurogenic.

7. Such a widespread distribution of altered autonomic tone suggests aberration of the function of the integrative centres of cardiovascular control.

8. Evidence is presented of a possible psychosomatic origin of these changes in some cases.
The Intrinsic Brain Iso-Renin-Angiotensin System in the Rat: Its Possible Role in Central Mechanisms of Blood Pressure Regulation
Authors: Ganten D. , Hutchinson J. S. , Schelling P.
Published: August 2015

1. Angiotensin is produced by the intrinsic iso-renin-angiotensin system.

2. Angiotensin is secreted into the cerebrospinal fluid of nephrectomized rats.

3. Angiotensin in cerebrospinal fluid elevates systemic blood pressure.

4. Rats with hereditary diabetes insipidus are virtually non-responsive to intraventricular angiotensin.

5. Angiotensin II is elevated in the cerebrospinal fluid of spontaneously hypertensive rats.

6. An intraventricular perfusion of the angiotensin II receptor-blocking agent P 113 decreases blood pressure in spontaneously hypertensive rats.
Effect of Prostaglandins (E2 and A2) on the Enzymatic Reaction of Human Renin in Isolated Homologous System and with Added Normal and Hypertensive Plasma
Authors: Eggena P. , Barrett J. , Sambhi M.
Published: August 2015

1. Prostaglandin E2 significantly inhibits the renin reaction in whole plasma as well as in the isolated system of semi-purified human renin and human renin substrate. The inhibitory effect of prostaglandin A2 was less marked in whole plasma and absent in the isolated system.

2. The inhibitory effect of prostaglandin E2 was more marked in normal than hypertensive plasma and was maximal at the lowest concentration used. In hypertensive plasma the maximal inhibitory effect was achieved at tenfold higher concentrations.

3. In normal plasma prostaglandin E2 does not affect the rate of product formation (k5 = k6), but inhibits the overall renin reaction by decreasing the total amount of available enzyme-substrate and enzyme-substrate modifier complex (K2K3).

4. In hypertensive plasma prostaglandin E2 acts as a potential accelerator of the rate of product formation (k6k5). In the range of substrate concentration employed, the apparent inhibitory effect is explained by an even greater lack of available complex (K2K3). This behaviour in hypertensive plasma is consistent with the presence of an additional modifier (? activator).
Renal Kallikrein Content of Spontaneously Hypertensive Rats
Authors: Favaro S. , Baggio B. , Antonello A. , Zen A. , Cannella G. , Todesco S. , Borsatti A.
Published: August 2015

1. The kallikrein content of kidneys from spontaneously hypertensive and normal rats at birth and at age 37 days was determined.

2. Kallikrein values were significantly lower in the hypertensive rats.

3. It is suggested that the lowered kallikrein may be related to the development of hypertension.
The Actions of Bradykinin and Eledoisin in the Canine Isolated Kidney: Relationships to Prostaglandins
Authors: McGiff J. C. , Itskovitz H. D. , Terragno N. A.
Published: August 2015

1. The effects of two vasodilator polypeptides, bradykinin and eledoisin, were studied in isolated blood-perfused canine kidneys before and after administration of indomethacin, an inhibitor of prostaglandin synthesis. Bradykinin, but not eledoisin, releases renal prostaglandins.

2. Before administration of indomethacin, bradykinin decreased urinary osmolality and increased free water clearance, whereas eledoisin did not affect the excretion of solute-free water. After administration of indomethacin, the renal vasodilator action of bradykinin was reduced but the vasodilator action of eledoisin was unaffected.

3. Fractional excretion of sodium was not affected by bradykinin before but was increased after administration of indomethacin. Reduction in glomerular filtration rate contributed to changes in sodium excretion produced by bradykinin and eledoisin.

4. The release of prostaglandins from the kidney by bradykinin amplifies the renal vasodilator action of the kinin and possibly mediates its effect on excretion of solute-free water.
Location of Aldosterone-Producing Adenomas by the Determination of Plasma Aldosterone in Adrenal Vein or Renal Vein Blood
Authors: Fukuchi S. , Takenouchi T. , Nakajima K. , Watanabe H. , Sugita A.
Published: August 2015

1. Aldosterone-producing adenomas were located before operation in eighteen patients by comparison of aldosterone concentrations in blood obtained by percutaneous catheterization of the adrenal vein or renal vein. The concentration of aldosterone in the venous effluent from the adrenal glands containing adenomas was significantly greater than in the venous effluent from contralateral glands.

2. Catheterization of the adrenal vein is, however, technically difficult. The location of adrenal adenomas was also possible by analysis of blood from the renal vein.

3. If the concentrations of aldosterone in blood from the left renal vein were higher than those from the right, the existence of a left adrenal adenoma was suggested. A high value in plasma, obtained from the inferior vena cava above the entry of the right adrenal vein, showed a right adrenal adenoma. This procedure identified very small functional adenomas which could not be demonstrated radio-graphically, or seen or palpated at surgery.

4. It was concluded that differential aldosterone measurement after percutaneous bilateral adrenal vein or renal vein catheterization can be used as a definitive test for the location of an aldosterone-producing adenoma, where this is uncertain.
Pituitary-Adrenal Response to Static Exercise in Man
Authors: Few J. D. , Imms F. J. , Weiner J. S.
Published: August 2015

1. Changes in plasma concentrations of catecholamines and Cortisol were measured before and after static exercise performed by the subject pushing with both legs against a strain-gauge bar. No marked changes in plasma catecholamine were observed but plasma Cortisol increased after the subject pushed for 3 min at 50% of maximum force.

2. Holding a 20 kg weight for 5 min in one hand caused a rise in plasma Cortisol and in plasma ACTH but no changes in growth hormone were observed.
Studies on the Nature of Complexes Formed by Copper with Human Alimentary Secretions and Their Influence on Copper Absorption in the Rat
Authors: Gollan J. L.
Published: August 2015

1. Human gastrointestinal secretions formed soluble copper complexes when labelled in vitro with 64Cu.

2. Copper-binding substances of low molecular weight were demonstrated in the saliva, gastric juice and secretin-stimulated duodenal aspirate of normal subjects by dialysis and gel-chromatography studies.

3. The nature of the copper complexes formed by secretions obtained from patients with Wilson's disease was similar to that of complexes formed by secretions of normal subjects.

4. Bile contained a copper-binding fraction of high molecular weight which was more concentrated in gall-bladder than hepatic bile. Between pH 5 and pH 8, this component had a greater binding affinity for copper than the other alimentary secretions or EDTA at a concentration of 10 mmol/l.

5. Absorption of 64Cu from 64Cu-labelled saliva, gastric juice or l-histidine solution (100 mmol/l) administered intraduodenally into groups of rats was similar to that observed in a control series given [64Cu]cupric acetate in sodium chloride solution. In contrast, the absorption of 64Cu from labelled hepatic and gall-bladder bile was significantly reduced.

6. The results suggest that dietary copper forms soluble complexes with the alimentary secretions and that these complexes influence absorption of the metal according to their molecular size. The net uptake of ingested copper from the gut lumen may represent a balance between the influence of dietary chelates, low-molecular-weight ligands in the alimentary secretions and a macromolecular copper-binding complex of bile.
Intrarenal Platelet Consumption in the Diffuse Proliferative Nephritis of Systemic Lupus Erythematosus
Authors: Clark W. F. , Lewis M. L. , Cameron J. S. , Parsons V.
Published: August 2015

1. Platelet survival and an index of the localization of platelets in the kidney were studied in patients with the proliferative nephritis of systemic lupus erythematosus, either focal or diffuse, and in control subjects. Platelet survival was reduced in patients with proliferative lupus nephritis, more in those with diffuse rather than focal renal involvement.

2. The index of renal platelet localization in patients with diffuse proliferative nephritis suggested an intrarenal platelet consumption not found in other groups.

3. A patient with the classical platelet autoantibody disease, idiopathic thrombocytopenic purpura, also showed reduced platelet survival but localization of platelets was in the spleen rather than the kidney.

4. Intrarenal platelet consumption in diffuse proliferative lupus nephritis may be an epiphenomenon of pre-existing scarring or platelet aggregation secondary to immune complex-formation, which contributes to the progressive sclerosing lesions of this form of nephritis.
Effect of Diazoxide on Renal Handling of Sodium in the Rat
Authors: Fine L. G. , Weber H.
Published: August 2015

1. To assess whether diazoxide-induced sodium retention is due to a direct renal action of the drug, independent of its systemic haemodynamic effects, diazoxide was infused directly into one renal artery of hydropenic rats. During the infusion period there was a small fall in mean systemic arterial blood pressure. There were no significant changes in the clearances of inulin or p-aminohippurate by either kidney.

2. Absolute and fractional excretion of sodium were unchanged on the non-infused side. On the side of infusion, there was a significant increase in absolute and in fractional sodium excretion.

3. Thus natriuresis rather than sodium retention seems to be the direct renal effect of diazoxide and may be related to its vasodilator properties.
Plasma Catecholamines, Plasma Renin Activity and Plasma Aldosterone in Tetraplegic Man, Horizontal and Tilted
Authors: Mathias C. J. , Christensen N. J. , Corbett J. L. , Frankel H. L. , Goodwins T. J. , Peart W. S.
Published: August 2015

1. Plasma catecholamines, plasma renin activity, plasma aldosterone and haematocrit were measured in four subjects with physiologically complete cervical spinal cord transections, before, during and after head-up tilt to 45° for 30 min. Plasma catecholamines were measured in five normal male volunteers in the supine position and after head-up tilt to 45° for 10 min.

2. After 10 min of head-up tilt, the plasma noradrenaline rose 14% in the tetraplegic patients and 115% in the control subjects. These findings indicate a failure of sympathetic activity in response to head-up tilt in the tetraplegic patients, probably caused by interruption of pathways by which the brain normally controls sympathetic outflow.

3. In the tetraplegic patients the resting plasma renin activities were above normal, and rose more quickly and greater on head-up tilt than in published studies of normal subjects. It is likely that the renal baroreceptors are important in the control of renin release.

4. In the tetraplegic patients, there was a late rise in plasma aldosterone which was probably due to the elevation in plasma renin activity.
Evidence for Active Transport of Tripeptides by Hamster Jejunum in Vitro
Authors: Addison Jill M. , Burston D. , Payne J. W. , Wilkinson S. , Matthews D. M.
Published: August 2015

1. This paper describes the uptake by rings of everted hamster jejunum in vitro of three peptides with structural features making them resistant to hydrolysis, glycylsarcosylsarcosine, glycylsarcosylsarcosylsarcosine and β-alanylglycylglycine.

2. Glycylsarcosylsarcosine was taken up by a saturable mechanism and accumulated intact in the intracellular compartment of the intestinal wall, apparently against an electrochemical gradient. Its uptake was reduced by Na+-replacement, anoxia and metabolic inhibitors. It was concluded that uptake of this peptide was the result of Na+-dependent active transport.

3. Glycylsarcosylsarcosylsarcosine was very poorly taken up and its uptake did not appear to be the result of active transport.

4. β-Alanylglycylglycine appeared intact in the intracellular compartment of the intestinal wall on a substantial scale though it was not concentrated. No satisfactory evidence of uptake by a saturable mechanism was obtained. Uptake was, however, inhibited by anoxia, 2,4-dinitrophenol and Na+-replacement. Reasons are given for supposing that uptake of this peptide may be the result of Na+-dependent active transport by the same carrier as that utilized by glycylsarcosylsarcosine.

5. The results suggest that provided that they escape brush-border hydrolysis, tripeptides, like dipeptides, are actively transported into the absorptive cells of the intestinal mucosa, but that the ability of these cells to take up peptides by an active mechanism is unlikely to extend to tetrapeptides.
Effect of Intravenous Frusemide on Plasma Renin Concentration: Suppression of Response in Hypertension
Authors: Padfield P. L. , Allison M. E. M. , Brown J. J. , Lever A. F. , Luke R. G. , Robertson C. C. , Robertson J. I. S. , Tree M.
Published: August 2015

1. Intravenous frusemide produced in normal subjects a prompt rise of plasma renin concentration which correlated with urinary sodium.

2. The renin response to frusemide was suppressed in patients with primary hyperaldosteronism.

3. In patients with low-renin hypertension and normal renin essential hypertension, the renin response to frusemide was similarly suppressed.

4. Suppression of the renin response to frusemide is therefore a feature of hypertension not confined to patients with primary hyperaldosteronism and low-renin hypertension.

5. Thus low-renin hypertension does not appear to constitute a distinct diagnostic entity.

6. It is suggested that suppression of the renin response is part of a long-term renal adaptation to high blood pressure.
The Effect of External Potassium Concentration on Leucocyte Cation Transport in Vitro
Authors: Hilton P. J. , Edmondson R. P. S. , Thomas R. D. , Patrick J.
Published: August 2015

1. Sodium and potassium transport rates in human leucocytes were measured in vitro at different external potassium concentrations.

2. At nominally zero external potassium concentrations, the ouabain-sensitive sodium efflux was reduced to less than 20% of its maximum value. There was evidence that under these conditions a ouabain-sensitive sodium-sodium exchange occurs.

3. Both total and ouabain-insensitive potassium influx increased with increasing external potassium concentration. The ouabain-sensitive potassium influx showed saturation.

4. Ouabain-insensitive potassium efflux was also stimulated by increasing the external potassium concentration, suggesting significant potassium-potassium exchange at physiological external potassium concentrations.
A Comparison of Natriuresis after Oral and Intravenous Sodium Loading in Sodium-Depleted Man: Evidence for a Gastrointestinal or Portal Monitor of Sodium Intake
Authors: Lennane R. J. , Carey R. M. , Goodwin T. J. , Peart W. S.
Published: August 2015

1. Dietary sodium reduction in man is followed by rapid conservation of sodium by the kidneys. The rapidity of this response suggests that the gastrointestinal tract is involved in early recognition of changes in sodium intake or in mediation of the compensatory response.

2. In order to test the hypothesis, 100 mmol of sodium was given to normal volunteers in balance on a low-sodium diet (5 mmol/24 h): the dose was given either orally or intravenously.

3. Those who received their sodium orally excreted it more rapidly than those who received it intravenously and the difference was most marked in the first 8 h after the dose.

4. This finding is consistent with the presence of an input receptor for sodium in the gastrointestinal tract.
Urinary Excretion of 17-Oxosteroids in Hereditary Coproporphyria
Authors: Paxton J. W. , Moore M. R. , Beattie A. D. , Goldberg A.
Published: August 2015

1. Urinary 17-oxosteroid conjugates were measured by gas-liquid chromatography in five patients with hereditary coproporphyria.

2. Three patients were in an acute attack and showed significantly increased excretion of sulphate or glucuronide conjugates of aetiocholanolone. There was increased excretion of several other related steroids but no consistent pattern was apparent.

3. In the two patients in remission, excretion of urinary 17-oxosteroids was not increased.

4. The ratio of total urinary aetiocholanolone to androsterone (5β:5α) was found to be significantly elevated for the three patients in an acute attack. Serial measurements were made in two of these patients and showed a highly significant linear correlation between this ratio and the urinary content of δ-aminolaevulic acid and porphobilinogen.

5. These observations suggest the involvement of the 17-oxosteroids, especially aetiocholanolone, in the pathogenesis of hereditary coproporphyria.
The Role of Baroreceptors and Chemoreceptors in the Regulation of the Cerebral Circulation
Authors: James I. M. , MacDonell Lindsay A.
Published: August 2015

1. Ten experiments, each using two dogs, were performed to evaluate the effect of chemoreceptor and baroreceptor activity on the cerebral circulation.

2. The carotid bifurcation areas were vascularly isolated bilaterally and perfused with arterial blood from a second animal.

3. Bilateral vagotomy interrupted stimuli from the aortic group of receptors.

4. Administration of 5% carbon dioxide to the donor animal resulted in an increase in cerebral (cortical) blood flow in the recipient.

5. A change in the arterial perfusion pressure from the donor resulted in a reciprocal change in the cerebral blood flow of the recipient. These changes were abolished by sectioning the sinus nerves.
The Influence of Potassium on the Renal Vasculature and the Adrenal Gland, and Their Responsiveness to Angiotensin II in Normal Man
Authors: Hollenberg N. K. , Williams G. , Burger B. , Hooshmand I.
Published: August 2015

1. The effect of modifying potassium intake on arterial plasma renin activity, angiotensin II and aldosterone concentrations, renal blood flow and their responses to exogenous angiotensin II has been assessed in twenty-six normal subjects.

2. Reduced potassium intake was associated with a significant increase in circulating renin activity and angiotensin II concentration and a significant reduction in renal blood flow. Conversely, a high potassium intake was associated with a significant increase in plasma aldosterone concentration and renal blood flow without alteration in plasma renin activity or angiotensin II concentration.

3. Reduced potassium intake decreased both the renal vascular and the adrenal response to infused angiotensin II. Conversely, an increased potassium intake enhanced the responsiveness of both systems.

4. The results suggest an important influence of potassium-induced renin-angiotensin system responses on both the renal vasculature and adrenal glomerulosa cell in normal man.
The Early Effects of Intravenous Frusemide on Central Haemodynamics, Venous Tone and Plasma Renin Activity
Authors: Hesse B. , Nielsen I. , Lund-Jacobsen H.
Published: August 2015

1. Nine patients with clinically unimportant heart disease or benign essential hypertension were given frusemide intravenously during right-heart catheterization.

2. Pressures in both atria decreased rapidly and in parallel. The magnitude of the pressure decrease was clearly related to decrease in plasma volume loss.

3. Plasma renin activity increased significantly after 5 min (P < 0·01), but did not correlate with plasma volume loss.

4. Venous tone in the forearm was unchanged.

5. It is concluded that the pressure reduction was secondary to plasma volume depletion through diuresis and that increased plasma renin activity was mainly caused by intrarenal changes.
The Meaning of Dopamine β-Hydroxylase in Essential Hypertension
Authors: Alexandre J. M. , London G. M. , Chevillard C. , Lemaire P. , Safar M. E. , Weiss Y.
Published: August 2015

1. Resting plasma dopamine β-hydroxylase (DBH) activity and haemodynamic parameters were studied in untreated borderline (twenty-nine) and permanent (twenty-seven) essential hypertensive patients. DBH was also measured in sixty-three apparently healthy subjects.

2. Mean DBH values were not significantly different between the groups.

3. Cardiac output, cardiopulmonary blood volume and the cardiopulmonary blood volume/total blood volume ratio (CPBV/TBV) were significantly higher in borderline than in permanent hypertensive patients.

4. In borderline hypertensive patients, plasma DBH activity was directly correlated with diastolic arterial pressure and with values of cardiac output, cardiopulmonary blood volume and CPBV/TBV ratio. No such correlations could be observed in the permanent hypertensive group.

5. These results suggest that plasma DBH activities in borderline hypertension mainly depend on the sympathetic activity responsible for the haemodynamic variations. Contrariwise, plasma DBH activities in permanent essential hypertensive patients appear to reflect other factors.
The Stimulation of Renin Secretion by Non-Vasocontrictor Infusions of Adrenaline and Noradrenaline in the Isolated Rat Kidney
Authors: Vandongen R. , Greenwood Dianne M.
Published: August 2015

1. The effect of adrenaline and noradrenaline on renin secretion in the isolated perfused rat kidney was examined. The doses of catecholamines used were such that renal vasoconstriction and therefore increases in renal perfusion pressure were avoided. Under these conditions adrenaline and noradrenaline significantly increased renin secretion rates, compared with control experiments in which no catecholamine was infused.

2. Mean renal perfusion pressure during both adrenaline and noradrenaline infusion paralleled the control study by showing a progressive fall.

3. Administration of phenoxybenzamine did not impair the stimulation of renin secretion by adrenaline whereas this was prevented by racemic propranolol.

4. These observations suggest that catecholamines stimulate renin secretion by an intrarenal effect which is largely independent of changes in renal perfusion pressure. It is postulated that the beta-adrenoceptors mediating renin secretion are an integral component of the renin-producing cell.
Variations in Thyroid Function and Sleep in Healthy Young Men
Authors: Johns M. W. , Masterton J. P. , Paddle-Ledinek J. E. , Patel Y. C. , Winikoff D. , Malinek M.
Published: August 2015

1. The total serum thyroxine, tri-iodothyronine resin uptake, total plasma protein concentration and the free thyroxine index (FTI) were determined repeatedly, at 07.15, 13.00 and 22.30 hours over 4 days, in six healthy young men.

2. There was a significant diurnal variation in the total serum thyroxine concentration but this reflected changes in the binding capacity of serum proteins and in the total plasma protein concentration which could be explained by changes of posture. The FTI, and presumably therefore the free thyroxine concentration, varied very little with the time of day.

3. The FTI varied significantly from day to day in three of the six subjects, presumably as a result of changes in thyroxine secretion because the serum binding capacity did not vary.

4. The subjects' sleep at night was assessed by electro-encephalogram. On days when the FTI was highest for a particular subject his sleep was more fragmented by spontaneous awakenings, the amount of rapid-eye-movement sleep was reduced and that of delta-wave sleep was increased, implying that variations in thyroid function over a period of a few days in healthy subjects can be of physiological significance. The cause of these variations is uncertain.
The Pattern of Venous Drainage of Surgically Created Side-to-Side Arteriovenous Fistulae in the Human Forearm
Authors: Jamison J. P. , Wallace W. F. M.
Published: August 2015

1. The forearm and hand circulation in nine patients with a surgically created side-to-side fistula between the radial artery and a nearby superficial vein in the lower forearm has been investigated.

2. Dilated veins on the dorsum of the hand communicated with the fistula without intervening valvular obstruction. Skin temperature of both forearm and hand was greater on the side with the fistula in all cases.

3. Inflation of an occlusion cuff distal to the fistula markedly reduced apparent fistular flow.

4. It is concluded that the fistulae result in increased blood flow to the hand by retrograde flow from the fistula into the hand veins. Hand as well as forearm must be included in the plethysmographic measurement of blood flow in such cases.
The Role of the Colon in Urea Metabolism in Man
Authors: Gibson J. A. , Park N. J. , Sladen G. E. , Dawson A. M.
Published: August 2015

1. The urea content of ileostomy effluent has been measured by the urease method as an indirect estimate of the urea concentration in the lumen of the normal ileum.

2. The plasma disappearance of intravenously administered [14C]urea was used to study intestinal urea breakdown. Normal subjects on high and low protein diets and patients with either excised (i.e. with ileostomies) or excluded colons were studied.

3. The 24 h intestinal urea breakdown was considerably greater than the quantity of urea estimated to be entering the colon from the ileum and across the colonic mucosa.

4. Intestinal urea breakdown increased with increase in dietary protein and decreased with, but was not abolished by, exclusion or excision of the colon.

5. Our results suggest that the colonic lumen is not the only site of intestinal ureolysis and that significant quantities of urea must be broken down either at a juxtamucosal site or in the ileum.
The Effect of Chelating Agents on Cellular Iron Metabolism
Authors: White G. P. , Bailey-Wood R. , Jacobs A.
Published: August 2015

1. The effect of iron chelators on iron uptake, ferritin and total protein synthesis was studied in cultured Chang cells. Desferrioxamine depressed ferritin synthesis and completely inhibited iron uptake by ferritin protein. Rhodotorulic acid reduced iron uptake by the cells but had little effect on ferritin synthesis. Diethylenetriamine pentaacetic acid produced complete inhibition of iron uptake and all protein synthesis. 2,3-Dihydroxybenzoic acid (2,3-DHB) had no effect in this system.

2. When 2,3-DHB was incubated with a liver homogenate, its subsequent addition to a Chang cell culture resulted in depression of ferritin synthesis, iron uptake into the protein and some depression of total protein synthesis. Pretreatment of rhodotorulic acid did not affect its properties.

3. Non-ferritin iron in the Chang cell cytosol was dialysable, available for binding to transferrin and formed chelates which appeared, on gel chromatography, to be of low molecular weight. Gel chromatography of cytosol after incubation of the cells with chelating agents showed non-ferritin iron to be in a similar form.

4. Loss of non-ferritin iron from the cells occurred only when the transferrin in the medium was unsaturated. In the presence of chelating agents non-ferritin iron was lost from the cells even when transferrin was 100% saturated.

5. The results confirm the presence of an intracellular labile iron pool which is available for chelation, and demonstrate that different iron chelators have different metabolic effects.
The Haemodynamic Effects of Metabolic Acidosis in the Rat
Authors: Yudkin J. , Cohen R. D. , Slack Barbara
Published: August 2015

1. The effect of metabolic acidosis of 4–6 h duration on cardiac output, blood pressure, heart rate, and hepatic and renal blood flow has been studied in the rat.

2. In anaesthetized rats, blood pressure and heart rate fell linearly with blood pH in both sham-operated and nephrectomized rats. There was no significant difference between the two groups in the effect of acidosis on either variable.

3. Cardiac output showed a significant fall with increasing acidosis in the conscious rat.

4. Estimated hepatic blood flow in conscious rats showed a significant positive correlation with blood pH in both sham-operated and nephrectomized animals. There was no significant difference in estimated hepatic blood flow between the two groups of animals at any blood pH.

5. In conscious rats, increasing acidosis caused a progressive decrease in estimated renal blood flow.

6. It is concluded that the increase in the previously described apparent renal contribution to lactate removal in the acidotic rat cannot be explained by any circulatory effect mediated by the kidney. The possible relevance of the findings to lactate homeostasis is discussed.
The Effect of Repeated Phlebotomy on Bilirubin Turnover, Bilirubin Clearance and Unconjugated Hyperbilirubinaemia in the Crigler—Najjar Syndrome and the Jaundiced Gunn Rat: Application of Computers to Experimental Design
Authors: Berk P. D. , Scharschmidt B. F. , Waggoner Jeanne G. , White S. C.
Published: August 2015

1. A multicompartmental model of erythrokinetics and bilirubin production has been developed to predict the consequences of chronic phlebotomy on daily bilirubin turnover.

2. Control values for four physiological variables including bilirubin turnover were determined in a 20-year-old woman with type I congenital non-haemolytic jaundice (Crigler—Najjar syndrome). With these base-line data, the model predicted the following changes during phlebotomy: a 34% fall in bilirubin turnover; a 240% increase in the haemoglobin content of bone-marrow erythroid precursors; a 25% fall in the half-life of 51Cr-labelled erythrocytes; a characteristic alteration of the erythrocyte survival curve after labelling with [2-14C]glycine.

3. On the assumption, previously validated in normal volunteer subjects and patients with Gilbert's syndrome, that hepatic bilirubin clearance was independent of turnover and would therefore remain unchanged, a fall in plasma unconjugated bilirubin concentration during phlebotomy from 436 to 282 μmol/l was expected.

4. Accordingly, the patient underwent phlebotomy 350 ml/week for 2 months, and 500 ml/week during an additional 3 months. Appropriate studies during phlebotomy confirmed each of the predictions in paragraph 2 above. In particular, turnover fell by 31%. Unexpectedly, plasma unconjugated bilirubin remained essentially unchanged. Analogous results were observed in phlebotomized jaundiced Gunn rats.

5. Kinetic studies in both the patient and the rats demonstrated that the failure of plasma unconjugated bilirubin to fall in parallel with bilirubin turnover resulted from a prolongation of the terminal half-life of radioactively labelled bilirubin and a fall in bilirubin clearance in every instance.

6. These studies indicate that (a) in congenital non-haemolytic jaundice, bilirubin clearance is uniquely influenced by bilirubin turnover and (b) compartmental modelling and kinetic studies are useful for predicting and interpreting the results of both physiological experiments and experimental therapeutic regimens.
The Relation between Functioning Parietal Cell and Gastrin Cell Masses in Two Groups of Duodenal Ulcer Patients
Authors: Byrnes D. J. , Lam Shiu Kum , Sircus W.
Published: August 2015

1. Serum gastrin concentrations before and after a standardized meal were determined in twenty-eight patients with duodenal ulcer and in ten normal control subjects.

2. In response to pentagastrin, thirteen of the duodenal ulcer subjects secreted acid within the limits of normal and fifteen secreted in excess.

3. The differences in the basal serum gastrin concentrations between the three groups, normal subjects, acid ‘normosecretors’ and hypersecretors were not statistically significant but that of the hypersecretors was suggestively low.

4. The integrated gastrin response and peak gastrin responses to meals were higher in duodenal ulcer patients with normal acid secretion than in the hypersecretors but the values for the latter were not different from normal subjects.

5. Stabilization of intragastric pH by infusion into the antrum of sodium bicarbonate during the test meal response period did not alter these differences between the two ulcer patient groups.

6. A significant inverse correlation exists between the maximal acid output and the integrated gastrin response in both normal subjects and hypersecreting duodenal ulcer patients.

7. The evidence (a) supports the existence of an inverse relationship between the functioning parietal cell and gastrin cell masses, (b) shows the gastrin response in normosecreting ulcer subjects to be inappropriately high, and (c) suggests that excessive vagotonia exerts trophic effects upon both parietal cell mass and gastrin cell mass.
Effect of Vasopressin on Plasma Volume and Renin Release in Man
Authors: Khokhär A. M. , Slater J. D. H. , Forsling Mary L. , Payne N. N.
Published: August 2015

1. Arginine vasopressin was infused into seven healthy young male volunteers at 12·5 and 25 units/min for 1 h at each dose. Plasma renin activity fell sharply and progressively in each subject. The mean fall was 47% and 66% of the initial value at the end of the lower and higher rates of arginine vasopressin infusion respectively; over 70% of the observed fall in plasma renin activity occurred at the end of the first infusion period.

2. The majority of the plasma arginine vasopressin concentrations achieved were within the physiological range observed after fluid deprivation and orthostatic stress in man, particularly at the lower rate of infusion.

3. There was no change of arterial pressure, despite a slight bradycardia at the lower rate of infusion; at the higher rate of infusion, there was only a very slight pressor response.

4. There was a concomitant and significant fall of plasma protein concentration and peripheral venous packed cell volume without any significant change of plasma sodium concentration or plasma osmolality, implying an expansion of plasma volume.

5. The results indicate that, in man, physiologically relevant amounts of arginine vasopressin suppress the rate of renin secretion indirectly by increasing the plasma volume at the expense of the extravascular fluid volume.
The Renal Handling of Insulin and Thyroid Hormones in Normal Man
Authors: Fine A. , Thomson R. M. , Jones J. V. , Murray R. G. , Tweddle A. , Gray C. E.
Published: August 2015

1. The renal extraction of insulin and thyroid hormones T3 and T4 was studied in man by right renal vein catheterization.

2. The mean renal extraction of insulin was 0·46, suggesting that the right renal vein should be utilized in comparable studies.

3. No renal extraction of thyroid hormones was detected.
The Encephalopathic Action of Five-carbon-atom Fatty Acids in the Rabbit
Authors: Teychenne P. F. , Walters I. , Claveria L. E. , Calne D. B. , Price Jane , Macgillivary B. B. , Gompertz D.
Published: August 2015

1. Five-carbon-atom organic acids (C-5 acids) have been administered intravenously to rabbits with ventriculocisternal perfusion and continuous electroencephalographic recording (EEG). The concentration of the acids in the cerebrospinal fluid (CSF) perfusate have been compared with changes in integrated low-frequency activity in the EEG.

2. The C-5 acids investigated were those accumulating in inborn errors of metabolism, i.e. isovaleric acid, β-methylcrotonic acid, tiglic acid and α-keto- and α-hydroxy-isovaleric acid. Their activity was compared with that of valeric acid.

3. Valeric acid and isovaleric acid produced coma and pronounced increase in slow-wave electrical activity and these changes paralleled the increase in concentration of the acids in the CSF perfusate.

4. The concentration of β-methylcrotonic acid and tiglic acid in the CSF perfusate reached values comparable with valeric acid and isovaleric acid but showed less encephalopathic activity. An interaction between β-methylcrotonic acid and isovaleric acid was observed.

5. Although the concentrations of α-ketoisovaleric acid and α-hydroxyisovaleric acid rose to the lesser extent in the CSF perfusate, changes in reusability of the animal and in the EEG recording were demonstrated.

6. It is concluded that all the C-5 acids tested have encephalopathic activity although this is lessened by the presence of either a double bond or an oxygenated functional group.
The Effect of Insulin on Adenosine 3′:5′-Monophosphate and Guanosine 3′:5′-Monophosphate Concentrations in Human Plasma
Authors: Siddle K. , Davies C. J. , Shetty K. J. , Elkeles R. S.
Published: August 2015

1. The action of insulin on plasma cyclic nucleotide concentrations in normal human subjects has been studied after intravenous injection, alone and in combination with glucagon.

2. After injection of insulin alone there was an initial small, though not significant, decrease in plasma cyclic AMP at 15 min followed by an increase to more than twice the initial concentration at 30 min. The increase was absent when hypoglycaemia was lessened by infusion of glucose after insulin injection.

3. Injection of insulin caused no significant change in plasma cyclic GMP concentration, whether or not glucose was infused after the hormone.

4. Glucagon (3–300 nmol, 10–1000 μg), caused a dose-dependent increase in plasma cyclic AMP concentration. The rise in plasma cyclic AMP produced by 3 or 30 nmol of glucagon was not significantly modified by simultaneous injection of insulin (44 nmol; 6 units).
Effect of Inhibition of Gluconeogenesis on Ammonia Production in the Perfused Rat Kidney
Authors: Ross B. D.
Published: August 2015

1. Gluconeogenesis from lactate or from glutamine is inhibited by 90–100% by sodium quinolinate (1 mmol/l) or 3-mercaptopicolinate (150 nmol/l) in the perfused rat kidney. l-Tryptophan is not metabolized and is without effect.

2. Lactate uptake and glucose production are inhibited to the same degree by 3-mercaptopicolinate in the kidneys of well-fed or starved rats.

3. Inhibition of gluconeogenesis from glutamine (1 mmol/l) by 3-mercaptopicolinate is accompanied by 50% inhibition of ammonia production, and 34% inhibition of glutamine uptake, in the kidneys of acidotic rats. Ammonia production from glutamine was not inhibited in kidneys from non-acidotic rats.

4. It is concluded that the increased rate of gluconeogenesis from glutamine which occurs in acidotic rats is an essential and primary event regulating all of the increase in ammonia formation.
Haemodynamic Studies in Dogs with Chronic Bile-Duct Ligation
Authors: Shasha S. M. , Better O. S. , Chaimovitz C. , Doman J. , Kishon Y.
Published: August 2015

1. Dogs with bile-duct ligation retain salt and water and form ascites. The present study was undertaken to examine the role of haemodynamic factors in the aetiology of this sodium retention.

2. Haemodynamic studies were performed in five dogs before and 5 weeks after bile-duct ligation.

3. After the operation there was an insignificant fall in mean arterial pressure, a significant rise in mean cardiac index and a significant fall in mean total peripheral resistance.

4. It is concluded that heart failure is not a factor in renal sodium retention of the dog with bile-duct ligation, since the central venous pressure was not elevated.

5. The haemodynamic pattern and the tendency to salt retention in the dog with chronic bile-duct ligation closely resemble findings reported in patients with cirrhosis of the liver, and it is suggested that oedema formation in patients with cirrhosis of the liver and dogs with chronic bile-duct ligation shares a common aetiology.
Release of Colony-Stimulating Activity from the Isolated Perfused Rat Liver
Authors: Howell A. , Cooksley W. G. E. , Danpure C. J.
Published: August 2015

1. Colony-stimulating activity appeared in the perfusate of the isolated rat liver during perfusions with either whole rat blood, rat plasma or an artificial perfusate of Eagle's medium and albumin.

2. Dialysable inhibitors of colony formation were also released during perfusions.

3. Colony-stimulating activity in artificial perfusate could be enhanced by the addition of rat plasma in vitro. Concentrations of cycloheximide that inhibited albumin synthesis by the liver did not inhibit the release of colony-stimulating activity.
The Disappearance of Enzyme—Inhibitor Complexes from the Circulation of Man
Authors: Ohlsson K. , Laurell C.-B.
Published: August 2015

1. Complexes of human trypsin and human granulocyte elastase with α1-anti-trypsin and α2-macroglobulin were isolated and injected intravenously into human volunteers.

2. The elimination of α2-macroglobulin complexes with trypsin and elastase followed single-exponential functions with half-lives of 9 and 12 min respectively. The complexes showed no tendency to dissociate.

3. Complexes of α1-anti-trypsin with trypsin persisted in the circulation much longer, with a half-life of 3·5 h; complexes of α1-anti-trypsin with elastase had an intermediate half-life of 1 h.

4. Dissociation was observed of α1-anti-trypsin complexes with transfer of trypsin and elastase to α2-macroglobulin.

5. Dialysable radioactivity appeared in the urine soon after the injection of α2-macroglobulin complexes, which suggested a breakdown of complexes by cells in the reticuloendothelial system. Radioactivity over the liver achieved maximum values within 30–40 min after the injection of α2-macroglobulin complexes but not until 50–70 min after the injection of α1-anti-trypsin complexes.

6. These results support the concept of a key position for α2-macroglobulin in the protective mechanisms against endogenous proteases.
Casual, Basal and Supplemental Blood Pressures in 519 First-Degree Relatives of Substantial Hypertensive Patients and in 350 Population Controls
Authors: Smirk F. Horace
Published: August 2015

1. The casual blood pressure is the sum of the relatively stable basal pressure taken under defined conditions of rest and the labile supplemental pressure (casual minus basal), which represents the response to the current degree of physical, mental and probably metabolic stimulation.

2. The basal and supplemental blood pressures behave differently and it seems likely that different factors are involved in their pathogenesis.

3. The 5 and 8 years follow-up mortality is closely related to the basal pressure but not to the supplemental pressure.

4. The rise with age in the basal blood pressure is greater in the relatives of substantial hypertensive patients than in population control subjects.

5. Above the age group 30–39 years there is an increase in the rate of rise of the mean basal blood pressure with age among the first-degree relatives of hypertensive patients. In a population control group an acceleration in the rate of rise of the mean basal blood pressure with age also occurs but a decade or more later than in the relatives of hypertensive patients.

6. In males the mean supplemental pressures (systolic and diastolic) do not rise appreciably with age and the mean supplemental pressures of first-degree relatives and control subjects do not differ appreciably.

7. In females the mean supplemental pressures rise with age but, except after age 60 years, the pressure rise in first-degree relatives is only a little greater than in control subjects.

8. When hypertensive patients with similar casual blood pressures are compared the basal blood pressures are higher in patients with glomerulonephritis than in essential hypertensive patients.

9. In the first-degree relatives of substantial hypertensive patients high-ranking basal blood pressures occur much more frequently than in general population control subjects.

10. The close resemblance of the blood pressures in like twins indicates that genetic or familial factors have an important influence on blood pressure, and on the occurrence of frank hypertension.
Intracellular Acid-Base Heterogeneity in Nucleated Avian Erythrocytes
Authors: Bone J. M. , Verth A. , Lambie Anne T.
Published: August 2015

1. Intracellular hydrogen ion activity, [H+]i, was estimated in human erythrocytes and in nucleated avian erythrocytes from measurements of the distribution of ammonia and 5,5′-dimethyloxazolidine-2,4′-dione (DMO) between intracellular and extracellular fluid.

2. In human erythrocytes there was no difference between values for [H+]i derived from measurements of either DMO or ammonia.

3. In avian erythrocytes, [H+]i(ammonia) was consistently greater than [H+]i(DMO), indicating significant acid—base heterogeneity of the intracellular water. The degree of heterogeneity was assessed by reference to a theoretical model of two compartments of equal size.

4. Experiments with nuclei isolated from avian erythrocytes suggested that DMO is not bound to nucleoproteins, and that the nucleus may be more acidic than the cytoplasm.
The Response of Arginine Vasopressin and Plasma Renin to Postural Change in Normal Man, with Observations on Syncope
Authors: Davies Roy , Slater J. D. H. , Forsling Mary L. , Payne Nadia
Published: August 2015

1. Fourteen mildly hydropenic normal volunteers were slowly tilted at a constant rate from the horizontal to the 85° head-up position in order to study the interrelationship between plasma arginine vasopressin concentration, plasma renin activity and the change of plasma volume.

2. Nine subjects did not develop vaso-vagal symptoms and were studied for 45–60 min. Arginine vasopressin rose biphasically in all subjects: a small initial rise, which was seen at 3 min and persisted for 30 min, was followed by a striking rise between 30 and 45 min, when the fall of plasma volume had reached its maximum (17%).

3. Plasma renin activity reached a maximum at 30 min but fell by 45 min, as plasma concentration of arginine vasopressin rose.

4. Five subjects developed vaso-vagal symptoms 4–24 min after reaching 85° when the study was terminated. A striking increase of arginine vasopressin concentration was seen within 4 min of syncope, but there was no change of plasma osmolality, cortisol concentration or renin activity.
Influence of Sodium Restriction upon Two Models of Renal Hypertension
Authors: Thurston H. , Swales J. D.
Published: August 2015

1. Restriction of dietary salt intake does not affect the development or maintenance of hypertension in rats with unilateral renal ischaemia whether the contralateral kidney is present (Goldblatt 2 model) or not (Goldblatt 1 model).

2. Acute dietary salt depletion induces a similar loss of sodium and fall in body weight with little change in blood pressure in both normal and hypertensive rats.

3. Excision of the ischaemic kidney in rats with short-term (< 50 days) Goldblatt 2 hypertension restores the mean blood pressure to normal, whereas Goldblatt 1 hypertensive rats show only a partial response. Previous salt depletion of this model enhances the blood pressure response to nephrectomy.

4. Sodium retention plays no part in the development or maintenance of Goldblatt 2 kidney hypertension. However, although sodium retention is normally involved in the Goldblatt 1 model, hypertension can develop in the absence of dietary sodium.